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13 Jan 2020	Early onset or syndromic epilepsy v2.0	AFF3	Louise Daugherty Tag watchlist was removed from gene: AFF3.
13 Jan 2020	Early onset or syndromic epilepsy v2.0	AFF3	Louise Daugherty commented on gene: AFF3
12 Jan 2020	Early onset or syndromic epilepsy v2.0	TET3	Konstantinos Varvagiannis gene: TET3 was added gene: TET3 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: TET3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TET3 were set to https://doi.org/10.1016/j.ajhg.2019.12.007 Phenotypes for gene: TET3 were set to Global developmental delay; Intellectual disability; Macrocephaly; Growth abnormality; Seizures; Autistic behavior; Abnormality of movement; Abnormality of the face Penetrance for gene: TET3 were set to Complete Review for gene: TET3 was set to AMBER Added comment: Beck et al (2020 - DOI: https://doi.org/10.1016/j.ajhg.2019.12.007) report on individuals with monoallelic de novo or biallelic pathogenic TET3 variants. For both inheritance modes (AR/AD) DD/ID were among the observed features (mild-severe - individuals from families 2, 4 and 6 for whom presence of ID was not commented, relevance to the current panel is suggested from the developmental milestones in the supplement. One individual presented DD without ID). Other features included hypotonia (in 8), ASD/autistic features (in 5), seizures (2 unrelated subjects for each inheritance mode). Postnatal growth abnormalities were observed in many, in most cases involving head size (with/without abnormal stature) and few presented abnormal prenatal growth. Variable movement disorders were observed in some. Some facial features appeared to be more common (eg. long face, tall forehead, etc). Most were referred for their DD. Extensive prior genetic investigations had (mostly) come out normal (with possible contribution of a 16p11.2 dup in an individual with monoallelic variant or a 16q22 dup in another with biallelic TET3 variants). Monoallelic / biallelic variants in all subjects were identified following exome sequencing. TET3 encodes a methylcytosine dioxygenase (the TET family consisting of 3 enzymes, TET1, TET2, TET3). These enzymes are involved in DNA demethylation through a series of reactions beginning with the conversion of 5-methyl cytosine [5mc] to 5-hydromethylcytosine [5hmC]. 5 individuals from 3 families (1/3 consanguineous) harbored biallelic missense variants. 5 different missense variants were observed. Heterozygous parents appeared to be mildly affected (eg. having learning difficulties, etc). 6 individuals from 5 families harbored monoallelic variants [3 truncating (of which 2 localizing in the last exon), 2 missense SNVs]. In one family the variant was inherited from a similarly affected parent. In all other cases the variant had occured de novo. No additional TET3 variants were identified, with the limitations of WES. All missense mutations, whether observed in individuals with biallelic or monoallelic variants, were located within the catalytic domain or - for a single variant (NM_001287491.1:c.2254C>T / p.Arg752Cys) - adjacent to it. Functional studies were carried out only for (all) missense variants observed in individuals with biallelic variants. Conversion of 5mC to 5hmC is the first step in DNA demethylation. In HEK293 cells overexpressing either wt or variants, production of 5hmc was measured. 4/5 missense variants evaluated demonstrated a defect in converting 5mC to 5hmC, Arg752Cys being an exception (as also predicted by its localization). DD/ID and abnormal growth are also features of disorders of the epigenetic machinery (DNA methylation machinery, histone machinery, chromatin remodelers, other chromatin-associated proteins). Similarly to TET3, both monoallelic and biallelic variants in KDM5B, encoding for another component of the epigenetic machinery, have been identified in individuals with ID. Mouse models discussed by the authors [several Refs provided though not here reviewed] : The gene has been shown to be highly expressed in oocytes, zygotes and neurons and to play a role in demethylation of the paternal genome after fertilization. (From the MGI: 'mice inheriting a null allele from a germ cell conditional null mother display impaired reprogramming of the paternal genome resulting in reduced embryo viability'). Beck et al also note that Tet3 inhibition or depletion in differentiated neurons can impact synaptic function [PMIDs cited: 25915473, 24757058, 26711116]. Sources: Literature
12 Jan 2020	Early onset or syndromic epilepsy v2.0	PIGP	Konstantinos Varvagiannis edited their review of gene: PIGP: Added comment: Please consider upgrading this gene to Green. In a recent study, Vetro et al. (2020 - https://doi.org/10.1212/NXG.0000000000000387) identified 4 additional affected individuals with severe EIEE, belonging to a large inbred family. Following extensive genetic investigations (all of which were non-diagnostic) these subjects were found to harbor in homozygosity the frameshift variant also reported in the 2 previous studies (NM_153681.2:c.456delA / p.Glu153AsnfsTer34 or NM_153682.2:c.384delA / p.Glu129AsnfsTer34). Reduced expression of the GPI-anchor protein CD16 was demonstrated in granulocytes of affected individuals.; Changed publications: 28334793, 31139695, https://doi.org/10.1212/NXG.0000000000000387
10 Jan 2020	Early onset or syndromic epilepsy v2.0	CACNA2D2	Louise Daugherty commented on gene: CACNA2D2
10 Jan 2020	Early onset or syndromic epilepsy v2.0	CACNA2D2	Louise Daugherty Tag watchlist was removed from gene: CACNA2D2.
07 Jan 2020	Early onset or syndromic epilepsy v2.0	ASTN1	Zornitza Stark gene: ASTN1 was added gene: ASTN1 was added to Genetic epilepsy syndromes. Sources: Expert list Mode of inheritance for gene: ASTN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ASTN1 were set to 29706646; 27431290; 26539891 Phenotypes for gene: ASTN1 were set to Intellectual disability; epilepsy; cortical malformations Review for gene: ASTN1 was set to GREEN gene: ASTN1 was marked as current diagnostic Added comment: Three families reported as part of large cohorts albeit proposing multiple novel candidate genes with minimal detail and no functional validation. Sources: Expert list
07 Jan 2020	Early onset or syndromic epilepsy v2.0	ASNS	Zornitza Stark gene: ASNS was added gene: ASNS was added to Genetic epilepsy syndromes. Sources: Expert list Mode of inheritance for gene: ASNS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ASNS were set to Asparagine synthetase deficiency, MIM# 615574 Review for gene: ASNS was set to GREEN Added comment: Encephalopathy, including seizures is a feature of this metabolic condition. Sources: Expert list
07 Jan 2020	Early onset or syndromic epilepsy v2.0	APC2	Zornitza Stark reviewed gene: APC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31585108; Phenotypes: Cortical dysplasia, complex, with other brain malformations 10, MIM#618677; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
07 Jan 2020	Early onset or syndromic epilepsy v2.0	ADRA2B	Zornitza Stark reviewed gene: ADRA2B: Rating: RED; Mode of pathogenicity: None; Publications: 24114805, 21937992; Phenotypes: Cortical myoclonus and epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
07 Jan 2020	Early onset or syndromic epilepsy v2.0	ADAM22	Zornitza Stark gene: ADAM22 was added gene: ADAM22 was added to Genetic epilepsy syndromes. Sources: Expert list Mode of inheritance for gene: ADAM22 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAM22 were set to 27066583; 30237576 Phenotypes for gene: ADAM22 were set to Epileptic encephalopathy, early infantile, 61, MIM# 617933 Review for gene: ADAM22 was set to AMBER Added comment: Two families reported; the second one as part of a large consanguineous cohort. Sources: Expert list
05 Jan 2020	Early onset or syndromic epilepsy v2.0	RNF113A	Konstantinos Varvagiannis gene: RNF113A was added gene: RNF113A was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: RNF113A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: RNF113A were set to 25612912; 31880405; 31793730; 29133357; 30506991; 15256591; 24026126; 23555887 Phenotypes for gene: RNF113A were set to ?Trichothiodystrophy 5, nonphotosensitive, 300953 Penetrance for gene: RNF113A were set to Complete Review for gene: RNF113A was set to GREEN Added comment: The gene has been reviewed for the ID panel. Seizures have been reported in 4 affected males from 3 families. From the ID panel: Nonphotosensitive trichothiodystrophy-5 (TTD5 - #300953) is caused by mutation in the RNF113A gene on Xq24. DD, ID and seizures are part of the phenotype in males. (Several) heterozygous females have not been reported to exhibit these features (DD/ID/seizures) although a single female in the first report had speech/motor delay and learning difficulties. Corbett et al (2015 - PMID: 25612912) reported on 2 cousins with profound ID and epilepsy among other principal features of the disorder. Linkage analysis (probably low(?) LOD score) localized the gene to a 7.75 Mb region on Xq and subsequent Sanger and exome sequencing identified an RNF113A stopgain variant in both (NM_006978.2:c.901C>T / p.Q301). Other X-chr variants did not segregate with the disorder. Previously sequencing of other trichothiodystrophy genes (in both) and CMA (X-chromosome BAC array / ISCA CMA) were non-diagnostic. The variant in this family was identified in a previous study (Tarpey et al 2009 - PMID: 19377476) but was 'incorrectly' discarded at the time due to a sequencing error in a control DNA sample (analysis repeated by Corbett et al). The same variant was also reported in 2 fetuses in a later report (PMID: 31793730). Mendelsohn et al (2019 - PMID: 31880405) reported on 2 unrelated affected males. The 1st presented with severe DD/ID (independent walking at 7y, single words/non-verbal with with special educational needs at 11y), seizures as well as typical features of the disorder. Metabolic work-up (incl. 7-DHCR) and genetic testing (Allagile, PFIC genes, CMA) were non-diagnostic. Duo WES revealed a frameshift variant [c.903_910delGCAGACCCA / p.(Gln302fs12)] inherited from the mother. Maternal XCI was completely skewed (100:0). The 2nd individual (briefly reported as REQ18-0616 by Monies et al - PMID: 31130284) presented global DD and seizures along with all other core features of the disorder at the age of 16m. Karyotype was normal. Exome revealed a frameshift variant [NM_006978.3:c.897_898delTG / p.(Cys299)]. Further evidence is based on the role of the RNA113A, being involved in mRNA splicing (/spiceosome function) [Gatti da Silva et al 2018 - PMID: 30506991 & many other Refs] as well in DNA repair (E3 ubiquitin-protein ligase in a mechanism for sensing DNA damage induced by alkylation) [Brickner et al 2017 - PMID: 29133357]. In the latter study, LCLs from individuals harboring Q301 were shown to be hypersensitive to an alkylating agent (MMS) which was also the case for an RNF113A knockdown cell line. The cells had reduced ASCC alkylation repair complex foci formation, which was rescued upon reconstitution of patient cells with wt RNF113A. Animal models : Disruption of rnf113a in zebrafish resulted among others in small head and underdeveloped gut (PMID cited : 15256591 - Amsterdam et al) similar to the microcephaly observed in several individuals and/or abnormal gut development/diarrhoea reported in few. Knockdown of the Drosophila ortholog (mdlc) led to reduced proliferation of neuroblasts. Neuronal differentiation was initiated but not completed. Expression of the full-length human gene rescued the CNS defects (discussed by Mendelsohn et al citing PMID: 24026126 - Carney et al). RNA-seq data from the same study were analyzed by Corbett et al, and differentialy expressed genes were enriched for genes involved in DNA damage response and repair. Knockdown of RNF-113 in C.elegans sensitises cells to UVA-induced DNA damage. RNF-113 was shown to be involved in interstrand DNA crosslink repair and interact with a RAD51C homolog (PMID cited: 23555887 - Lee et al). [Please consider upgrade/inclusion in other relevant panels eg. the 'Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome panel' where the gene has red rating]. Sources: Literature
02 Jan 2020	Early onset or syndromic epilepsy v2.0	MTHFS	Konstantinos Varvagiannis gene: MTHFS was added gene: MTHFS was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: MTHFS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MTHFS were set to 30031689; 31844630; 22303332; https://doi.org/10.1007/978-3-642-40337-8_10 Phenotypes for gene: MTHFS were set to Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination, 618367 Penetrance for gene: MTHFS were set to Complete Review for gene: MTHFS was set to GREEN Added comment: Biallelic pathogenic MTHFS variants cause Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination (# 618367). The gene encodes 5,10-Methenyltetrahydrofolate synthetase which catalyzes conversion of 5-formyltetrahydrofolate (5-FTHF or folinic acid) to 5,10-methenyltetrahydrofolate (5,10-MTHF). At least 3 unrelated individuals have been reported. The phenotype appears to be relevant to both epilepsy and ID gene panels and the role of variants/the gene supported by enzymatic activity studies, 5-FTHF accumulation, 5,10-MTHF levels (low/low-normal), the role of folate metabolism pathway overall and some supporting (metabolic) evidence from the mouse model. --- Rodan et al (2018 - PMID: 30031689) reported on 2 individuals both presenting with microcephaly, severe global DD, epilepsy, progressive spasticity and cerebral hypomyelination upon MRI imaging. Short stature was also feature in both. The 1st patient was an 8-year-old male who following exome sequencing was found to harbor 2 missense variants each inherited from a carrier parent. (NM_006441.3:c.434G>A / p.R145Q and c.107T>C / p.L36P). A further AFG3L2 indel was not felt to fit with his phenotype (and the onset of the related disorder appears to occur later). Previous investigations included extensive metabolic testing, CMA, Angelman syndrome methylation analysis, GFAP, POLG1, TYMP sequencing, mitochondrial genome analysis and an XL-ID gene panel (further suggesting relevance of this gene to the current panel) were all non-diagnostic. CSF 5-MTHF levels were initially on the low-normal range, subsequently found to be decreased (upon folinic acid supplementation) and later normalized upon use of another regimen. MTHFS activity was measured in control fibroblasts as well as fibroblasts from this individual, with the latter demonstrating no enzyme activity. Accumulation (30x elevation) of 5-FTHF (the substrate of MTHFS) was demonstrated in patient fibroblasts. The 2nd patient was a 11-year-old male with similar features incl. global DD (standing/walking/single words at/after 4 years of age, limited vocabulary and articulation upon last examination). Extensive metabolic work-up as well as genetic testing for an epilepsy panel, vanishing white matter disease gene panel, mitochondrial genome as well as specific gene sequencing (LAMA2, POLR3A, POLR3B) were all non-diagnostic. Trio exome revealed 2 MTHFS variants in trans configuration (c.484C>T / p.Q162X and c.434G>A / p.R145Q). --- Romero et al (2019 - PMID: 31844630) reported on a 4-year-old female with congenital microcephaly, severe global DD (nonverbal/nonambulatory at the age of 4), spasticity, epilepsy and cerebral hypomyelination. Extensive investigations prior to exome sequencing revealed macrocytic anemia, decreased CSF 5-MTHF and elevated neopterin, 2 CNVs of uncertain significance upon CMA with additional long ROH on chr15. Methylation studies were negative. The child was homozygous for c.220C>T / p.R74X (RefSeq is probably NM_006441.3. MTHFS lies on chr15. The parents were unrelated but came from the same town). There were no other candidate variants from the exome analysis. Both articles discuss extensively the role of the folate metabolism pathway overall in nucleic acid synthesis, AA metabolism, neurotransmitter synthesis, methylation as well as 5-FTHF / 5,10-MTHF in particular in myelin stabilization and DNA synthesis (eg. according to Romero et al. a defect in MTHFS would impair myelin production and also lead to decreased myelin stability). --- A book chapter cited by Rodan et al (in N. Blau et al. (eds.), Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases - DOI: 10.1007/978-3-642-40337-8_10) included limited details on a patient with 'MTHFS gene mutation'. This individual had early speech delay, seizures beginning in infancy, ID, autistic features, recurrent infections and was found to have very low CSF 5-MTHF levels. [Details in p169 and table 10.6 - p173]. --- In a mouse model reported by Field et al (2011 - PMID: 22303332), Mthfs was disrupted through insertion of a gene trap vector between the first 2 exons. Heterozygous [Mthfs(gt/+)] mice were fertile and viable. Mthfs protein levels were slightly but not statistically significantly reduced in tissues measured. No homozygous embryos were recovered following intercrosses of heterozygous mice, suggesting that Mthfs is an essential gene. Mouse embryonic fibroblasts from heterozygous mice [Mthfs (gt/+)] exhibited reduced de novo purine biosynthesis, but did not exhibit altered de novo thymidylate biosynthesis. Plasma folate levels were altered in heterozygous mice on a standard (/control) diet. [Please consider inclusion in other possibly relevant panels e.g. for metabolic disorders] Sources: Literature
31 Dec 2019	Early onset or syndromic epilepsy v2.0	PUM1	Konstantinos Varvagiannis gene: PUM1 was added gene: PUM1 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: PUM1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: PUM1 were set to 29474920; 30903679; 31859446 Phenotypes for gene: PUM1 were set to Global developmental delay; Intellectual disability; Seizures; Abnormality of the face; Ataxia; Cryptorchidism Penetrance for gene: PUM1 were set to unknown Review for gene: PUM1 was set to GREEN Added comment: 5 unrelated individuals with de novo pathogenic PUM1 variants have been reported in the literature. DD (5/5), ID (4/5 - relevant severity to the current panel), seizures (4/4 - absence/tonic-clonic, abnormal EEG) and variable other features (incl. facial dysmorphism, ataxia, cryptorchidism) appear to be part of the phenotype. 9 individuals with deletions spanning PUM1 and proximal genes presented similar features. [1] PMID: 29474920 - Gennarino et al (2018) [2] PMID: 30903679 - Bonnemason-Carrere et al (2019) [3] PMID: 31859446 - Voet et al (2019) [with review of the literature] SNVs in relevant individuals were identified by exome sequencing and were in all cases de novo. Arg1147Trp was a recurrent variant reported in 3 unrelated subjects with ID and seizures (Refs 1,2,3 / NM_001020658.1:c.3439C>T). A nonsense variant was reported in an additional one with DD, ID, seizures and additional features (c.2509C>T / p.Arg837* - Ref3). One individual with a de novo missense variant (c.3416G>A / p.Arg1139Trp) with DD and ataxia, though without ID was reported in Ref1. Details on 9 individuals with 0.3 - 5.6 Mb deletions spanning PUM1 and other genes are provided in Ref1. Features also included DD, ID, seizures, ataxia, etc. Extensive initial investigations were reported for individuals in Refs 2 and 3 (various investigations incl. karyotype, SNP-array, targeted sequencing of OPHN1, KANSL1 or of a small panel of ID genes, biopsies and/or metabolic work-up) to rule out alternative causes. These only revealed a likely benign CNV and a GRIA3 SNV of uncertain significance in the case of an individual harboring the recurrent Arg1147Trp variant [Ref2]. Role of the gene (from OMIM): Pumilio proteins, such as PUM1, negatively regulate gene expression by repressing translation of mRNAs to which they bind (Lee et al., 2016). A clinically significant PUM1 target is ataxin (ATXN1; 601556), mutation in which causes spinocerebellar ataxia-1 (SCA1; 601556). Variant studies: - Arg1147Trp was shown to be associated with normal PUM1 mRNA levels, but reduced (to ~43%) PUM1 protein levels in patient fibroblasts. ATXN1 mRNA and protein levels, as well as protein and/or mRNA levels of other PUM1 targets were shown to be increased (Ref1). - In Ref1, in vitro transfection assays with wt or mt PUM1 were performed in HEK293T cells to evaluate repression of ATXN1 and E2F3. While overexpression of wt and Arg1147Trp were able to reduce ATXN1 and E2F3 levels, Arg1139Trp was not able to repress ATXN1 or E2F3. - Upon overexpression in mouse hippocampal neurons, PUM1 missense mutations (among others Arg1139Trp and Arg1147Trp) were shown to alter neuronal morphology. Overall haploinsufficiency is the proposed mechanism for the disorder for which the acronym PADDAS is used (Pumilio1-associated developmental disability, ataxia and seizure). Milder mutations reducing PUM1 levels by 25% are associated with adult-onset ataxia without ID (PRCA or Pumilio1-related cerebellar ataxia) [Ref1]. Mouse models: The role of PUM1 was first suggested in mouse models where Pum1 mutations were shown to lead to a SCA1-like phenotype (PMID cited : 12086639 - Watase et al 2002) further shown to be caused by increased Atxn1 mRNA and protein levels (PMID cited : 25768905 - Gennarino et al 2015). The mouse model seems to recapitulate several of the features observed in affected individuals : Pum1 homozygous ko mice display among others hyperactivity, progressive cerebellar signs, spontaneous seizures as also observed in affected individuals (PMID cited : 25768905 - Gennarino et al 2015). Cryptorchidism was observed in 2 patients similar to testicular hypoplasia reported in Pum1 ko mice (PMID cited : 22342750 - Chen et al 2012). - Heterozygous mice were evaluated in Ref1 with 69% or 75% exhibiting spontaneous seizures by the end of 30 or 35 wks respectively, with abnormal EEG activity already by 16 wks. Additional individuals with PUM1 variants and a relevant phenotype of ID with or without seizures have been reported as part of the DDD study or as external submissions to Decipher and ClinVar : https://decipher.sanger.ac.uk/search?q=PUM1#research-variants/results [ DDD4K.01387 participant ] https://decipher.sanger.ac.uk/search?q=pum1#consented-patients/results [ external submission(s) ] https://www.ncbi.nlm.nih.gov/clinvar/variation/431110/ [ splice-site variant in an individual with ID submitted prior to the 1st publication on the disorder ] Sources: Literature
29 Dec 2019	Early onset or syndromic epilepsy v2.0	DLL1	Konstantinos Varvagiannis gene: DLL1 was added gene: DLL1 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: DLL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: DLL1 were set to 31353024 Phenotypes for gene: DLL1 were set to Global developmental delay; Intellectual disability; Morphological abnormality of the central nervous system; Seizures; Behavioral abnormality; Autism; Scoliosis Penetrance for gene: DLL1 were set to unknown Review for gene: DLL1 was set to AMBER Added comment: Gene added to the ID panel. Epilepsy has been reported in 6 unrelated individuals. Please consider inclusion with amber/green rating. ---- Heterozygous DLL1 pathogenic variants cause Neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures (# 618709). Fischer-Zirnsak et al (2019 - PMID: 31353024) reported on 15 affected individuals from 12 unrelated families. Most common features included DD/ID (12/14), ASD (6/14 - belonging to 6 families) or other behavioral abnormalities, seizures (6/14 - from 6 unrelated families) and various brain MRI abnromalities. As commented by OMIM (based on the same ref) "Cognitive function ranges from severely impaired to the ability to attend schools with special assistance". Among other features, scoliosis was observed in 4. The authors could not identify a distinctive facial gestalt. Variable initial investigations (where discussed/performed - also suggesting relevance to the current panel) included CMA, FMR1, FLNA, mitochondrial DNA analysis and metabolic work-up but had not revealed an alternative cause. The DLL1 variants were identified by WES (with the exception of a 122-kb microdeletion spanning DLL1 and FAM120B detected by CMA). Nonsense, frame-shift, splice-site variants in positions predicted to result to NMD were identified in most. One individual was found to harbor a missense variant (NM_005618.3:c.536G>T / p.Cys179Phe) and another the aforementioned microdeletion. The variant in several individuals had occurred as a de novo event. In 2 families, it was inherited from an also affected parent (an unaffected sib was non-carrier) while in 3 families parental studies were not possible/complete. In frame insertion of 4 residues was demonstrated for a splice site variant, from LCLs of the corresponding individual. For another individual, material was unavailable for mRNA studies. The missense variant affected a cysteine (of the DSL domain) conserved in all Notch ligands while AA changes affecting the same position of JAG1 (another Notch ligand) have been described in patients with Alagille s. Based on the variants identified and reports of deletions spanning DLL1 in the literature, haploinsufficiency is the proposed underlying mechanism. The gene has also a pLI of 1 and %HI of 4.65. DLL1 encodes the Delta-like canonical Notch ligand 1. Notch signaling is an established pathway for brain morphogenesis. Previous in vivo and in vitro studies have demonstrated the role of DLL1 in CNS. The gene is highly expressed in neuronal precursor cells during embryogenesis. Expression of Dll1 (and other molecules of the Notch signalling pathway) in an oscillatory/sustained pattern and cell-cell interactions important for this pathway have been demonstrated to play a role in neuronal differentiation. [Most discussed by Fischer-Zirnsak et al with several refs provided / also Gray et al., 1999 - PMID: 10079256 & OMIM]. Animal models as summarized by the authors: [Mouse] Loss of Dll1 in mice has been shown to increase neuronal differentiation, cause CNS hyperplasia and increased number of neurons (PMIDs cited: 9109488, 12397111, 20081190). Reduced Dll1 expression was associated with scoliosis and mild vertebral defects (cited PMIDs: 19562077, 14960495, 22484060 / among others Dll1 haploinsufficiency and dominant negative models studied). Scoliosis and vertebral segmentation defects were features in 4 and 1 individual, respectively in the cohort of 15. [Zebrafish] Homozygous mutations in dlA, the zebrafish ortholog, disrupted the Delta-Notch signaling and led to patterning defects in the hindbrain and overproduction of neurons (cited: 15366005). Sources: Literature
27 Dec 2019	Early onset or syndromic epilepsy v2.0	TFE3	Konstantinos Varvagiannis reviewed gene: TFE3: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30595499, 31833172, https://doi.org/10.1126/scisignal.aax0926; Phenotypes: Global developmental delay, Intellectual disability, Abnormality of skin pigmentation, Coarse facial features, Seizures; Mode of inheritance: Other
22 Dec 2019	Early onset or syndromic epilepsy v2.0	UGP2	Konstantinos Varvagiannis gene: UGP2 was added gene: UGP2 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: UGP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UGP2 were set to 31820119 Phenotypes for gene: UGP2 were set to Seizures; Global developmental delay; Intellectual disability; Feeding difficulties; Abnormality of vision; Abnormality of the face Penetrance for gene: UGP2 were set to Complete Review for gene: UGP2 was set to GREEN Added comment: Perenthaler et al. (2019 - PMID: 31820119) provide evidence that homozygosity for a variant abolishing the start codon of the UGP2 transcript (NM_001001521.1) encoding the predominant (short) protein isoform in brain, leads to a severe epileptic encephalopathy. This variant (chr2:64083454A>G / NM_001001521.1:c.1A>G - p.?) is also predicted to result in a substitution of a methionine at position 12 by a valine of the longer UGP2 transcript (NM_006759.3:c.34A>G - p.Met12Val). The 2 isoforms differ only by 11 amino acids at the N-terminal and are otherwise expected to be functionally equivalent. The authors provide details on 22 individuals from 15 families (some of which consanguineous). Features included intractable seizures (in all), absence of developmental milestones (in all), progressive microcephaly, visual impairment. The authors reported also presence of somewhat similar facial features. Some of these individuals passed away early. Previous work-up in several of them (incl. SNP-array, gene panel testing and metabolic investigations) had not revealed any abnormality, apart from ROH in some individuals. In all cases, the homozygous UGP2 SNV was the only P/LP variant for the neurodevelopmental phenotype following exome/genome sequencing. Segregation studies in affected/unaffected family members were compatible. Families came from the Netherlands (but mostly from) India, Pakistan and Iran. Presence of a region of homozygosity shared between individuals from different families suggested that the variant might represent a mutation that originated several generations ago (in the area of Balochistan). The variant is present 15x in gnomAD, only in heterozygous state (in Asian mostly, reported once in Ashkenazi Jewish or Europeans) [ https://gnomad.broadinstitute.org/variant/2-64083454-A-G ]. UGP2 encodes UDP-glucose pyrophosphorylase which is an essential enzyme in sugar metabolism, catalyzing conversion of glucose-1-phosphate to UDP-glucose. UDP-glucose, in turn, serves as precursor for production of glycogen by glycogen synthase. The authors provide several lines of evidence for a the role of the gene in the CNS as well as for the deleterious effect of the specific variant : - In patient fibroblasts total UGP2 levels were not signifficantly different compared to parent / control fibroblasts, the longer isoform being upregulated (and stable) when the shorter is missing. Immunocytochemistry demonstrated similar localization of UGP2 in the case of mutant or wt cells. Enzymatic activity (/capacity to produce UDP-glucose) was similar between homozygous mut, heterozygous and wt fibroblasts. - In H9-derived neural stem cells, Western Blot, RT-PCR and qRT-PCR suggested that the short isoform is the predominant one. (In embryonic stem cells, or fibroblasts the ratio between short and long isoform was lower). - Analysis of RNA-seq data from human fetal tissues suggested that the short isoform is the predominant in brain. - UGP2 was detected upon immunohistochemistry in fetal brain tissues from first to third trimester of pregnancy while Western Blot confirmed preferential expression of the shorter isoform. - Homozygous embryonic (ESC) or neural stem cells (NSC) for the variant (knock-in/KI) or for a frameshift variant (knock-out/KO) were generated. Study of NSCs demonstrated reduced total UGP2 protein expression upon Western Blot in the case of KI cells and depleted in KO ones. Transcriptome analysis did not show major transcriptome alterations in KI/KO ESCs compared to wt. In NSC KI/KO cells transcriptome alterations were observed compared to wt with upregulation among others of genes for synaptic processes and genes implicated in epilepsy. - The absence of UGP2 was shown to result in reduced ability of KO/KI NSCs to produce UDP-glucose, reduced capacity to synthesize glycogen under hypoxia (rescued in the case of KO cells by overexpression of wt or long isoform), defects of protein glycosylation as well as in increased unfolded protein response (/susceptibility to ER stress). These alterations are commented to be possibly implicated in pathogenesis of epilepsy, progressive microcephaly, etc. - A CRISPR-Cas9 zebrafish model leading with loss of ugp2a and hypomorphic ugp2b (the zebrafish homologs of UGP2) demonstrated abnormal behavior, reduced eye movements and increased frequency/duration of movements upon stimulation with a potent convulsant (suggestive of increased seizure susceptibility). - UGP knockout in drosophila is lethal while flies compound heterozygous for hypomorphic alleles are viable but show a movement defects due to altered synaptogenesis secondary to glycosylation defects (cited PMID: 27466186). - The authors make speculations as for the occurrence of a single variant (and not others) eg. absence of UGP2 (in the case of LoF variants affecting both isoforms) would possibly be incompatible with life, Met12Val being tolerable for the long transcript not affecting stability/enzymatic activity (which may not be the case for other substitutions affecting Met12), etc. Sources: Literature
18 Dec 2019	Early onset or syndromic epilepsy v2.0	ADPRHL2	Louise Daugherty Tag new-gene-name tag was added to gene: ADPRHL2.
18 Dec 2019	Early onset or syndromic epilepsy v2.0	ADPRHL2	Louise Daugherty commented on gene: ADPRHL2
15 Dec 2019	Early onset or syndromic epilepsy v2.0	KAT8	Konstantinos Varvagiannis gene: KAT8 was added gene: KAT8 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: KAT8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: KAT8 were set to 31794431 Phenotypes for gene: KAT8 were set to Global developmental delay; Intellectual disability; Seizures; Abnormality of vision; Feeding difficulties; Abnormality of the cardiovascular system; Autism Penetrance for gene: KAT8 were set to unknown Review for gene: KAT8 was set to GREEN Added comment: Heterozygous pathogenic missense KAT8 variants have been reported in individuals with DD, ID and epilepsy. Variants occurred as de novo events within the chromobarrel or the acetyltransferase domain and were all shown to affect H4K16 acetylation, as would be predicted by the gene's function (lysine acetyltransferase). Evidence from brain specific Kat8 knockout in mouse, supports the role of the gene in brain development. One similarly affected individual compound heterozygous for a nonsense and a missense variant (the former affecting subnuclear localization and the latter H4K16ac) was also reported, with carrier relatives being unaffected. Mutations in genes of the MSL/NSL complexes (with which KAT8 forms multisubunit complexes) or genes in other acetyltransferases of the same subfamily (MYST) as KAT8 cause neurodevelopmental disorders [Details provided below]. ----- Li et al. (2019 - PMID: 31794431) report on 8 unrelated individuals with heterozygous de novo pathogenic KAT8 variants, as well as an additional one compound heterozygous for a nonsense and a missense one. Overlapping phenotype consisted of DD/ID (8/8), seizures/epilepsy (6/8), brain MRI anomalies as well as presence of variable facial dysmorphic features. Less frequent features included abnormal vision (5/8), feeding difficulties (3/8), cardiac anomalies (3/8), autism (in 1). The (9th) individual with biallelic variants had similar phenotype of DD/ID, epilepsy, autism and dysmorphic facial features. Heterozygous parents and sister, the latter carrier for the missense variant, were all unaffected. All individuals had undergone exome sequencing, while extensive other investigations for at least 7/9 had only revealed variants of uncertain significance/contribution to the phenotype or were normal. KAT8 encodes lysine acetyltransferase 8, which acetylates histone H4 at lysine 16 (H4K16). It belongs to the MYST subfamily of lysine acetyltransferases, the other members of which include KAT6A, KAT6B (both involved in neurodevelopmental disorders) and KAT5. KAT8 forms two stoichiometric multisubunitcomplexes, one with the MSL complex and the other with the NSL. Mutations in genes encoding for subunits of the NSL or MSL complex (eg. KANSL1 and MSL3) are associated with neurodevelopmental disorders. Overall 6 missense SNVs were reported among the heterozygous patients, p.Tyr90Cys (NM_032188.2:c.269A>G) being a recurrent one seen in 3. The compound heterozygous patient had a missense (c.973C>T / p.Arg325Cys) and a nonsense variant (c.523A>T / p.Lys175*). All missense variants lied either in the chromobarrel domain or the acetyltransferase domain. Variants in the latter domain localized within the KAT8/Mof-specific region or - in the case of the compound heterozygous individual - within the acetyl-CoA binding motif. FLAG-tagged KAT8 (either wt or for all missense SNVs) was transfected in HEK293 cells with vectors for HA-tagged MSL proteins. While the nonsense variant was difficult to express, missense SNVs were expressed to similar levels to wt, promoted expression of MSL proteins but resulted in defective H4K16 acetylation and to a lesser extent H4K5 acetylation. As a result all missense variants impaired acetylation. This was also the case for chromobarrel domain variants, while expression of a KAT8 lacking the chromobarrel domain confirmed its ability to form complex with the MSL proteins and the impairment of H4K16 acetylation. The nonsense variant demonstrated abnormal subnuclear localization. The mouse model provides extensive evidence for the involvement of KAT8 in cerebral development. Cerebrum-specific Kat8 knockout mice presented postnatal growth retardation, hyperactivity/irritability, pre-weaning lethality, and cerebral hypoplasia upon autopsy. Loss of Kat8 reduced the number of neural stem and progenitor cells available for embryonic cerebrocortical development, impaired cell proliferation and stimulated apoptosis. The article also provides additional evidence from mouse model. Sources: Literature
15 Dec 2019	Early onset or syndromic epilepsy v2.0	RARS	Konstantinos Varvagiannis gene: RARS was added gene: RARS was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: RARS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RARS were set to 31814314; 28905880; 24777941 Phenotypes for gene: RARS were set to Leukodystrophy, hypomyelinating, 9 616140 Penetrance for gene: RARS were set to Complete Review for gene: RARS was set to GREEN Added comment: Biallelic pathogenic RARS1 variants cause Leukodystrophy, hypomyelinating, 9 (# 616140). The current review was based primarily on PMID: 31814314 (Mendes et al, 2019) providing details on 20 affected individuals from 15 families. 5 of these patients were included in a previous publication (Wolf et al, 2014 - PMID: 24777941) sharing authors with this study. Clinical presentation and severity can be highly variable. However, among the 15 patients of relevant age (5/20 deceased at an early age), ID was observed in 13 (in 6/13 mild-moderate, in 7/13 severe/profound). Epilepsy was reported in half (10/20) with seizures being refractory to treatment in most and the phenotype corresponding to an infantile epileptic encephalopathy. DD and seizures were the presenting feature in 7 and 5 patients respectively, while in other cases presenting features were less specific (eg. failure to thrive in 1/20, irritabilty in 2/20). As a result the gene appears to be relevant to both DD/ID and epilepsy panels. RARS1 encodes the cytoplasmic arginyl-tRNA synthetase 1, which is a component of the aminoacyl-tRNA synthetase complex (OMIM and Wolf et al, 2014 - PMID: 24777941). Aminoacyl-tRNA synthetases catalyze the aminoacylation ('charging') of tRNA by (with) their cognate amino acid. Utilisation of alternative initiation codons, from a single mRNA transcript, results in translation of a long and a short protein isoform (Zheng et al 2006 - PMID: 16430231). The long isoform is needed for the formation of the multi-synthetase complex (MSC), while the short is free in the cytoplasm and does not have any interaction with the MSC. The long isoform appears to be essential for protein synthesis (discussed with several refs provided in PMID: 28905880 - Nafisinia et al, 2017). The role of variants has been supported in several patients by additional studies - among others : [PMID 31814314] Impaired Arginyl-tRNA synthetase activity was demonstrated in fibroblasts from 3 patients. Activity was normal in one additional individual compound heterozygous for a variant affecting initiation codon and a missense one. Western blot however demonstrated presence mainly of the short protein isoform. The authors suggest that this isoform possibly contributed to enzymatic activity. The long isoform which is needed for the MSC complex was only represented by a faint band in the Western Blot of the same individual. [PMID: 28905880] Using fibroblasts from an affected subject homozygous for a missense variant (NM_002887.3:c.5A>G / p.Asp2Gly) and controls, a 75% reduction of the long isoform was shown upon WB. The short isoform was present at similar levels. As the N-terminus (of the long isoform) mediates interaction with the MSC (and AIMP1), assembly of the latter was 99% reduced in patient fibroblasts. Proliferation of patient fibroblasts was significantly reduced when cultured in a medium with limited arginine, a finding which was thought to reflect inefficient protein synthesis. Mutations in other genes encoding for aminoacyl-tRNA synthetases (eg. AARS1, VARS1) or scaffolding proteins of the multisynthetase complex (eg. AIMP1 and AIMP2) lead to neurodevelopmental disorders with overlapping phenotype [most genes rated green in both the ID and epilepsy panel]. Sources: Literature
10 Dec 2019	Early onset or syndromic epilepsy v2.0	AFF3	Konstantinos Varvagiannis changed review comment from: Voisin et al. (2019 - https://doi.org/10.1101/693937) report on 10 individuals with de novo missense AFF3 variants affecting a 9-amino-acid sequence (degron) important for the protein's degradation and summarize the phenotype of an additional individual previously described by Steichen-Gersdorf et al. (2008 - PMID: 18616733) with a 500 kb affecting only AFF3 (LAF4) and removing also this sequence. The phenotype of missense variants consisted of kidney anomalies, mesomelic dysplasia, seizures, hypertrichosis, intellectual disability and pulmonary problems and was overlapping with that of the deletion. [10 of 11 subjects exhibited severe developmental epileptic encephalopathy]. 9 probands harbored missense variants affecting the codon 258 while one individual had a variant affecting codon 260 [c.772G>T or p.Ala258Ser (x2), c.772G>A or p.Ala258Thr (x6), c.773C>T or p.Ala258Val (x1) and c.779T>G or p.(Val260Gly) (x1) - NM_001025108.1 / NP_001020279.1]. The deletion removed exons 4-13. AFF1-4 are ALF transcription factor paralogs, components of the transcriptional super elongation complex regulating expression of genes involved in neurogenesis and development. Using HEK293T cells expressing FLAG-tagged AFF3 (and AFF4) wt or mutants, accumulation of mutated forms was shown upon immunoblot. Aff3+/- and/or -/- mice exhibit skeletal defects. These were more pronounced in homozygous mice which demonstrated also some elements in favor of kidney dysfunction and/or metabolic deregulation and possible neurological dysfunction (signs of impaired hearing and diminished grip strength). Homozygous mice had CNS anomalies (enlarged lateral ventricles and decreased corpus callosum size) similar to some affected individuals, although these were not observed in another Aff3-/- model. Knock-in mice modeling the microdeletion and the Ala258Thr variant displayed lower mesomelic limb deformities and early lethality respectively [cited PMIDs : 21677750, 25660031, knock-in model was part of the present study]. Accumulation of the protein in zebrafish (by overexpression of the human wt AFF3 mRNA), led to morphological defects. Reanalysis of transcriptome data from previously generated HEK293T cell lines knocked down for AFF2, AFF3 and AFF4 by shRNAs (study) suggested that these transcription factors are not redundant. Finally, CHOPS syndrome (#616368) due to mutations of AFF4 also leading to increased protein stability presents a partially overlapping phenotype (incl. cognitive impairment) to that of AFF3. ---- In G2P, AFF3 is associated with Skeletal dysplasia with severe neurological disease (disease confidence : probable / ID and seizures among the assigned phenotypes). There is no associated phenotype in OMIM. ---- As a result this gene can be considered for inclusion in the epilepsy panel as green (relevant phenotype and severity, sufficient cases, evidence for accumulation similar to AFF4, animal models, etc) or amber (pending publication of the article). Sources: Literature --------------- Shimizu et al. (8/2019 - PMID: 31388108) describe an additional individual with de novo AFF3 missense variant. The phenotype overlaps with that summarized by Voisin et al. incl. mesomelic dysplasia with additional skeletal anomalies, bilateral kidney hypoplasia and severe DD at the age of 2.5 years. Seizures and pulmonary problems were not observed. Although a different RefSeq is used the variant is among those also reported by Voisin et al. [NM_002285.2:c.697G>A (p.Ala233Thr) corresponding to NM_001025108.1:c.772G>A (p.Ala258Thr)].; to: Voisin et al. (2019 - https://doi.org/10.1101/693937) report on 10 individuals with de novo missense AFF3 variants affecting a 9-amino-acid sequence (degron) important for the protein's degradation and summarize the phenotype of an additional individual previously described by Steichen-Gersdorf et al. (2008 - PMID: 18616733) with a 500 kb deletion affecting only AFF3 (LAF4) and removing also this sequence. The phenotype of missense variants consisted of kidney anomalies, mesomelic dysplasia, seizures, hypertrichosis, intellectual disability and pulmonary problems and was overlapping with that of the deletion. [10 of 11 subjects exhibited severe developmental epileptic encephalopathy]. 9 probands harbored missense variants affecting the codon 258 while one individual had a variant affecting codon 260 [c.772G>T or p.Ala258Ser (x2), c.772G>A or p.Ala258Thr (x6), c.773C>T or p.Ala258Val (x1) and c.779T>G or p.(Val260Gly) (x1) - NM_001025108.1 / NP_001020279.1]. The deletion removed exons 4-13. AFF1-4 are ALF transcription factor paralogs, components of the transcriptional super elongation complex regulating expression of genes involved in neurogenesis and development. Using HEK293T cells expressing FLAG-tagged AFF3 (and AFF4) wt or mutants, accumulation of mutated forms was shown upon immunoblot. Aff3+/- and/or -/- mice exhibit skeletal defects. These were more pronounced in homozygous mice which demonstrated also some elements in favor of kidney dysfunction and/or metabolic deregulation and possible neurological dysfunction (signs of impaired hearing and diminished grip strength). Homozygous mice had CNS anomalies (enlarged lateral ventricles and decreased corpus callosum size) similar to some affected individuals, although these were not observed in another Aff3-/- model. Knock-in mice modeling the microdeletion and the Ala258Thr variant displayed lower mesomelic limb deformities and early lethality respectively [cited PMIDs : 21677750, 25660031, knock-in model was part of the present study]. Accumulation of the protein in zebrafish (by overexpression of the human wt AFF3 mRNA), led to morphological defects. Reanalysis of transcriptome data from previously generated HEK293T cell lines knocked down for AFF2, AFF3 and AFF4 by shRNAs (study) suggested that these transcription factors are not redundant. Finally, CHOPS syndrome (#616368) due to mutations of AFF4 also leading to increased protein stability presents a partially overlapping phenotype (incl. cognitive impairment) to that of AFF3. ---- In G2P, AFF3 is associated with Skeletal dysplasia with severe neurological disease (disease confidence : probable / ID and seizures among the assigned phenotypes). There is no associated phenotype in OMIM. ---- As a result this gene can be considered for inclusion in the epilepsy panel as green (relevant phenotype and severity, sufficient cases, evidence for accumulation similar to AFF4, animal models, etc) or amber (pending publication of the article). Sources: Literature --------------- Shimizu et al. (8/2019 - PMID: 31388108) describe an additional individual with de novo AFF3 missense variant. The phenotype overlaps with that summarized by Voisin et al. incl. mesomelic dysplasia with additional skeletal anomalies, bilateral kidney hypoplasia and severe DD at the age of 2.5 years. Seizures and pulmonary problems were not observed. Although a different RefSeq is used the variant is among those also reported by Voisin et al. [NM_002285.2:c.697G>A (p.Ala233Thr) corresponding to NM_001025108.1:c.772G>A (p.Ala258Thr)].
10 Dec 2019	Early onset or syndromic epilepsy v2.0		Rebecca Foulger promoted panel to version 2.0
10 Dec 2019	Early onset or syndromic epilepsy v1.498		Rebecca Foulger Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS signed-off
09 Dec 2019	Early onset or syndromic epilepsy v1.497	TRAPPC4	Konstantinos Varvagiannis gene: TRAPPC4 was added gene: TRAPPC4 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: TRAPPC4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TRAPPC4 were set to 31794024 Phenotypes for gene: TRAPPC4 were set to Feeding difficulties; Progressive microcephaly; Intellectual disability; Seizures; Spastic tetraparesis; Abnormality of the face; Scoliosis; Cortical visual impairment; Hearing impairment Penetrance for gene: TRAPPC4 were set to Complete Review for gene: TRAPPC4 was set to GREEN Added comment: Van Bergen et al. (2019 - PMID: 31794024) report on 7 affected individuals from 3 famillies (only 1 of which consanguineous), all homozygous for a TRAPPC4 splicing variant. Overlapping features included feeding difficulties, progressive microcephaly, severe to profound developmental disability (7/7 - DD also prior to the onset of seizures / regression also reported in 3), epilepsy (7/7 - onset in the first year), spastic quadriparesis. Other findings in some/few incl. scoliosis, cortical visual and hearing impairment. Some facial features were shared (eg. bitemporal narrowing, long philtrum, open mouth with thin tented upper lip, pointed chin, etc). Brain imaging demonstrated abnormalities in those performed (among others cerebral with/without cerebellar atrophy). Work-up prior to exome sequencing was normal (highly variable incl. metabolic testing, CMA, MECP2, CDKL5, mitochondrial depletion studies, etc). Exome of affected individuals (and parents +/- affected sibs in some families) revealed a homozygous TRAPPC4 splicing variant [NM_016146.5:c.454+3A>G / chr11:g.118890966A>G (hg19)]. Sanger sequencing confirmed variant in affecteds, heterozygosity in parents and compatible genotypes with disease status in sibs/other members. Families were of Caucasian/Turkish and French-Canadian ethnicities. SNP array to compare haplotypes between affecteds in 2 families did not reveal a shared haplotype (/founder effect) and the variant is present in gnomAD (68/281054 - no hmz) in many populations (European/Asian/African/Latino) [https://gnomad.broadinstitute.org/variant/11-118890966-A-G]. mRNA studies in fibroblasts from an affected individual confirmed the splicing defect (2 RT-PCR products corresponding to wt and a shorter due to skipping of exon 3, the latter further confirmed by Sanger sequencing. The shorter transcript is not present in controls). qPCR revealed that the normal transript in patient fibroblasts was present at 6% of the level observed in control fibroblasts (or 54% in the case of a heterozygote parent compared to controls). Western blot in patient fibroblasts, revealed presence of full-length protein in significantly reduced levels compared to fibroblasts from carrier parents or controls. There was no band using an antibody targeting the N-terminal region of the protein prior to exon 3, suggesting that NMD applies (skipping of ex3 is also predicted to lead to frameshift). TRAPPC4 encodes one of the core proteins of the TRAPP complex. Use of different accessory proteins leads to formation of 2 distinct complexes (TRAPPII / III). The complex has an important role in intracellular trafficking. Both TRAPPII & TRAPPIII have a function in the secretory pathway, while complex III has a role also in autophagy. Core proteins are important for the complex stability. The TRAPP complex serves as a GEF for Ypt/Rab GTPases [several refs in article]. Mutations in genes for other proteins of the complex lead to neurodevelopmental disorders with associated ID ('TRAPPopathies' used by the authors / TRAPPC12, C6B, C9 green in the current panel). Western blot suggested that levels of other TRAPP subunits (TRAPPC2 or C12) under denaturing conditions, although PAGE/size exclusion chromatography suggested that the levels of fully-assembled TRAPP complexes were lower in affected individuals. Studies in patient fibroblasts showed a secretory defect (between ER, Golgi and the plasma membrane) which was restored upon lentiviral transduction with wt TRAPPC4 construct. Basal and starvation-induced autophagy were also impaired in patient fibroblasts (increased LC3 marker and LC3-positive structures / impaired co-localization with lysosomes) partly due to defective autophagosome formation (/sealing). TRAPPC4 is the human orthologue of the yeast Trs23. In a yeast model of reduced Trs23 (due to temperature instability) the authors demonstrated impaired assembly of the TRAPP core. The yeast model recapitulated the autophagy as well as well as the secretory defect observed in patient fibroblasts. Sources: Literature
09 Dec 2019	Early onset or syndromic epilepsy v1.497	SNX27	Konstantinos Varvagiannis gene: SNX27 was added gene: SNX27 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: SNX27 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SNX27 were set to 25894286; 31721175; 21300787; 23524343 Phenotypes for gene: SNX27 were set to Generalized hypotonia; Global developmental delay; Intellectual disability; Seizures Penetrance for gene: SNX27 were set to Complete Review for gene: SNX27 was set to AMBER Added comment: (From the ID panel) Evidence from 2 publications suggests that DD, ID and seizures are part of the phenotype of individuals with biallelic SNX27 pathogenic variants : --------- Damseh, Danson et al (2015 - PMID: 25894286) first reported on a consanguineous family with 4 affected sibs, homozygous for an SNX27 pathogenic variant. Features incl. hypotonia soon after birth, failure to thrive, severely delayed psychomotor development with no milestone acquisition, occurrence of myoclonic seizures with 3 individuals deceased early. Exome sequencing in one revealed a few candidate variants, with an SNX27 frameshift one [NM_030918.6:c.515_516del - p.(His172Argfs6) / absent from ExAC] being the only retained following Sanger segregation studies. Using fibroblasts from an affected individual, Western blot with an antibody which would also bind prior to the truncation site, was consistent with dramatically reduced/absent SNX27 truncated mutant protein. Protein levels of VPS35, a component of the retromer responsible for direct cargo binding (not mediated by a cargo adaptor as SNX27), were normal. --------- Parente et al (2019 - PMID: 31721175) reported on a 13-year-old male with motor and language delay, ADHD, ID (kindergarten academic level at the age of 13) and seizures with onset at the age of 9 years (GTC, with abnormal EEG and postical SV tachycardia). Variable physical findings were reported. White matter hyperintesities were noted upon initial brain MRI (but were less marked in subsequent ones). Initial genetic testing (Alexander's disease, CMA, FMR1) was normal. Exome revealed compound heterozygosity for 2 SNX27 variants (NM_030918.5/NM_001330723.1 both apply c.510C>G - p.Tyr170 and c.1295G>A - p.Cys432Tyr) each inherited from healthy carrier parents. There were no other potentially causative variants. A parental history of - isolated - late onset seizures was reported (so this individual may not be considered for the seizure phenotype here). The authors also reported on a further 31-year old affected male. This individual had infantile hypotonia, poor eye contact with subsequent significant DD, seizures (febrile/afebrile T-C with onset at the age of 14m) and ID estimated in the severe range. Variable - though somewhat different - physical findings were reported. Initial work-up included basic metabolic testing, standard karyotype, FISH for 15q11 and subtelomeric regions and PHF6 genetic testing - all normal. Exome (and subsequent Sanger confirmation/parental studies) revealed compound heterozygosity for a missense and a frameshift variant (c.989G>A / p.Arg330His and c.782dupT / p.Leu262Profs*6 same in NM_001330723.1, NM_030918.6). --------- SNX27 encodes sorting nexin 27, a cargo adaptor for the retromer. The latter is a multi-protein complex essential for regulating the retrieval and recycling of transmembrane cargos from endosomes to the trans-Golgi network or the plasma membrane [Lucas et al 2016 - PMID: 27889239 / McNally et al 2018 - PMID: 30072228]. As summarized by Parente et al, the encoded protein by regulating composition of the cell surface influences several processes eg. neuronal excitability, synaptic plasticity, Wnt signaling etc. It has been shown to interact with surface receptors and their ligands including GIRK channels, 5-HT4, ionotropic glutamate receptors (incl. NMDA- and AMPA-type receptors) and mGluR5 [several refs. provided]. Knockout of Snx27 in mice resulted in embryonic lethality (16% hmz of the 25% expected), severe postnatal growth retardation and death within the first 3 weeks. Snx27(+/-) mice have normal neuroanatomy but exhibit cognitive deficits (in learning and memory) and defects in synaptic function/plasticity with reduced amounts of NMDA and AMPA receptors (Cai et al - PMID: 21300787, Wang et al - PMID: 23524343). --------- There is no associated phenotype in OMIM/G2P. Sources: Literature
01 Dec 2019	Early onset or syndromic epilepsy v1.497	OXR1	Konstantinos Varvagiannis gene: OXR1 was added gene: OXR1 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: OXR1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: OXR1 were set to https://doi.org/10.1016/j.ajhg.2019.11.002 Phenotypes for gene: OXR1 were set to Central hypotonia; Global developmental delay; Delayed speech and language development; Intellectual disability; Seizures; Abnormality of the cerebellum Penetrance for gene: OXR1 were set to Complete Review for gene: OXR1 was set to GREEN Added comment: Wang et al (2019 - https://doi.org/10.1016/j.ajhg.2019.11.002 ) report on 5 individuals (from 3 families) with biallelic OXR1 LoF variants. Common features included hypotonia (4/5), severe global DD (5/5) and speech delay (5/5), ID (5/5), epilepsy (5/5) with cerebellar dysplasia/atrophy (5/5) and in some scoliosis. All were investigated by exome sequencing and were found to harbor biallelic loss-of-function variants (2 splice-site, a stopgain and a frameshift one) either in homozygosity (2 consanguineous families) or in compound heterozygosity. In all cases parental segregation studies were compatible and in one family, an unaffected sib shown to be carrier. Althouhgh OXR1 has been shown to affect several processes (among others DNA lesions induced by oxidative stress in E.coli, neuronal maintenance, mitochondrial morphology and DNA maintenance, etc), its mechanism of action is still not well defined. There are 6 RefSeq transcripts, the longest (NM_018002.3) encoding 3 protein domains (LysM, GRAM, TLDc). The TLDc domain is encoded by all transcripts. Identified variants affected (probably all - fig1D) transcripts expressed in the CNS, namely NM_018002.3, NM_001198532.1, NM_181354.4. The 3 transcripts not expressed in the CNS are NM_001198533.1, NM_001198534.1 and NM_001198535.1. Western blot with 2 different antibodies which would bind upstream of the truncation site failed to detect presence of truncated proteins in 2 affected individuals from 2 families. The Drosophila homolog of OXR is mustard (mtd). The authors provide evidence that loss of mtd is lethal. This was however rescued by expression of an 80kb fly BAC clone covering mtd, or the fly mtd-RH isoform cDNA, or a short human OXR1 cDNA containing only the TLDc domain or a human NCOA7 cDNA. The latter is another human mtd homolog which also contains the TLDc domain. As a result the TLDc domain compensated sufficiently for loss of mtd. Flies that survived displayed bang sensitivity and climbing defects the former assay being suggestive of susceptibility to seizures and the latter of impaired neurological/muscular function. The authors provided evidence that mtd is broadly expressed in the fly CNS. RNAi mediated mtd knockdown specific to neurons (elav/nSyb-GAL4 expression of mtd RNAi) led to lethal eclosion defects for RNAis targeting most (18)/all(23) mtd isoforms. Lifespan was increased upon expression of human OXR1 cDNA. Neuronal loss and vacuolization was demonstrated and additional experiments in R7 photoreceptors showed presence of aberrant lysosomal structures (autolysosomes, autophagosomes and/or endolysosomes). Aberrant lysosomal structures were also observed in fibroblasts from affected individuals (accumulation of lysosomes and/or presence of highly aberrant compartments with content typical of lysosomal dysfunction). Overall the data presented suggest a critical role for OXR1 in lysosomal biology. Although previous reports suggested that OXR1 is involved in oxidative stress resistance, studies performed by the authors suggested that oxidative stress is probably not the driver of the mutant fly defects. Sources: Literature
29 Nov 2019	Early onset or syndromic epilepsy v1.497	PCYT2	Ellen McDonagh reviewed gene: PCYT2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
28 Nov 2019	Early onset or syndromic epilepsy v1.497		Rebecca Foulger Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
28 Nov 2019	Early onset or syndromic epilepsy v1.496	WWOX	Rebecca Foulger Publications for gene: WWOX were set to Tabarki (2015) Ben-Salam (2015) Mignot (2015)
28 Nov 2019	Early onset or syndromic epilepsy v1.495	WWOX	Rebecca Foulger Phenotypes for gene: WWOX were changed from to Epileptic encephalopathy, early infantile, 28, 616211
28 Nov 2019	Early onset or syndromic epilepsy v1.494	WDR45	Rebecca Foulger Phenotypes for gene: WDR45 were changed from to Neurodegeneration with brain iron accumulation 5, 300894
28 Nov 2019	Early onset or syndromic epilepsy v1.493	WDR45	Rebecca Foulger Publications for gene: WDR45 were set to Saitsu et al (2013) Nat Genet. 45(4):445-9
28 Nov 2019	Early onset or syndromic epilepsy v1.492	STX1B	Rebecca Foulger Phenotypes for gene: STX1B were changed from to Generalized epilepsy with febrile seizures plus, type 9, 616172
28 Nov 2019	Early onset or syndromic epilepsy v1.491	STX1B	Rebecca Foulger Mode of inheritance for gene: STX1B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
28 Nov 2019	Early onset or syndromic epilepsy v1.490	SLC6A1	Rebecca Foulger Phenotypes for gene: SLC6A1 were changed from to Myoclonic-atonic epilepsy, 616421
28 Nov 2019	Early onset or syndromic epilepsy v1.489	SLC6A1	Rebecca Foulger Publications for gene: SLC6A1 were set to Carvill et al (2015) Am J Hum Genet 96(5): 808-15
28 Nov 2019	Early onset or syndromic epilepsy v1.488	PNPO	Rebecca Foulger Phenotypes for gene: PNPO were changed from to Pyridoxamine 5'-phosphate oxidase deficiency, 610090
28 Nov 2019	Early onset or syndromic epilepsy v1.487	NDUFS8	Rebecca Foulger Phenotypes for gene: NDUFS8 were changed from Mitochondrial complex I deficiency, nuclear type 2, 618222 to Mitochondrial complex I deficiency, nuclear type 2, 618222; Leigh syndrome due to mitochondrial complex I deficiency
28 Nov 2019	Early onset or syndromic epilepsy v1.486	NDUFS8	Rebecca Foulger Phenotypes for gene: NDUFS8 were changed from to Mitochondrial complex I deficiency, nuclear type 2, 618222
28 Nov 2019	Early onset or syndromic epilepsy v1.485	DNM1	Rebecca Foulger Mode of inheritance for gene: DNM1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
28 Nov 2019	Early onset or syndromic epilepsy v1.484	DNM1	Rebecca Foulger Publications for gene: DNM1 were set to EuroEPINOMICS-RES Consortium (2014) AJHG 95:1-11
28 Nov 2019	Early onset or syndromic epilepsy v1.483	DNM1	Rebecca Foulger Phenotypes for gene: DNM1 were changed from to Epileptic encephalopathy, early infantile, 31, 616346
28 Nov 2019	Early onset or syndromic epilepsy v1.482	CYFIP2	Rebecca Foulger Mode of pathogenicity for gene: CYFIP2 was changed from None to Other
28 Nov 2019	Early onset or syndromic epilepsy v1.481	CYFIP2	Rebecca Foulger Publications for gene: CYFIP2 were set to 29534297
28 Nov 2019	Early onset or syndromic epilepsy v1.480	CYFIP2	Rebecca Foulger Phenotypes for gene: CYFIP2 were changed from to Epileptic encephalopathy, early infantile, 65, 618008
28 Nov 2019	Early onset or syndromic epilepsy v1.479	CSTB	Rebecca Foulger Publications for gene: CSTB were set to
28 Nov 2019	Early onset or syndromic epilepsy v1.478	CSTB	Rebecca Foulger Phenotypes for gene: CSTB were changed from to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), 254800
28 Nov 2019	Early onset or syndromic epilepsy v1.477	PNPT1	Konstantinos Varvagiannis gene: PNPT1 was added gene: PNPT1 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: PNPT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PNPT1 were set to 31752325 Phenotypes for gene: PNPT1 were set to Combined oxidative phosphorylation deficiency 13, MIM 614932 Penetrance for gene: PNPT1 were set to Complete Review for gene: PNPT1 was set to GREEN Added comment: Reviewed for the intellectual disability panel. Seizures may be observed in affected individuals (details below). Please consider inclusion with amber / green rating. --- Biallelic PNPT1 pathogenic variants cause Combined oxidative phosphorylation deficiency 13 (MIM 614932). Despite phenotypic variability - common to disorders resulting from mitochondrial dysfunction - DD and ID of relevant severity to the current panel have been reported in several individuals published in the literature. Seizures may also be observed. Rius et al (2019 - PMID: 31752325) provide an overview of 24 affected individuals (7 new and 17 from previous studies). Neurodevelopmental features are summarized in fig.1 and additional details are provided in the supplement. Based on this review, seizures were present in 7 individuals (of the 18 for whom this information was available). PNPT1 encodes the mitochondrial polynucleotide phosphorylase, involved in the import of nuclear-encoded RNA to mitochondria. Loss of its activity has been shown to result in combined respiratory chain deficiency. However, as discussed by Rius et al and previous articles as well, OXPHOS studies in affected individuals may be normal or suggestive of only mild impairment due to tissue specificity and different assay methods used (eg. spectrophotometric vs dipstick activity assays). The same applies to lactate which was normal or mildly elevated in some affected individuals. Missense, pLoF function variants as well as a synonymous one leading to aberrant splicing (NM_033109.4:c.1818T>G) have been reported. Sources: Literature
27 Nov 2019	Early onset or syndromic epilepsy v1.477	SCAMP5	Ellen McDonagh Added comment: Comment on mode of pathogenicity: A dominant negative effect is predicted.
27 Nov 2019	Early onset or syndromic epilepsy v1.477	SCAMP5	Ellen McDonagh Mode of pathogenicity for gene: SCAMP5 was changed from Other to Other
27 Nov 2019	Early onset or syndromic epilepsy v1.476	SCAMP5	Ellen McDonagh Classified gene: SCAMP5 as Amber List (moderate evidence)
27 Nov 2019	Early onset or syndromic epilepsy v1.476	SCAMP5	Ellen McDonagh Added comment: Comment on list classification: Gene added by external Reviewer, and promoted to Amber due to review and overall evidence.
27 Nov 2019	Early onset or syndromic epilepsy v1.476	SCAMP5	Ellen McDonagh Gene: scamp5 has been classified as Amber List (Moderate Evidence).
26 Nov 2019	Early onset or syndromic epilepsy v1.475	TMX2	Konstantinos Varvagiannis gene: TMX2 was added gene: TMX2 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: TMX2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMX2 were set to 31586943; 31735293; 31270415 Phenotypes for gene: TMX2 were set to Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormal cortical gyration Penetrance for gene: TMX2 were set to Complete Review for gene: TMX2 was set to GREEN Added comment: This gene was reviewed for the intellectual disability panel. Epilepsy is part of the phenotype. Therefore green rating should be considered. From the ID panel : A recent report by Vandervore, Schot et al. following the previous review (Am J Hum Genet. 2019 Nov 12 - PMID: 31735293), provides further evidence that biallelic TMX2 mutations cause malformations of cortical development, microcephaly, DD and ID and epilepsy. As a result this gene should probably be considered for inclusion in the ID/epilepsy panels with green rating. Overall, 14 affected subjects from 10 unrelated families are reported in the aforementioned study. The majority had severe DD/ID (failure to achieve milestones, absent speech/ambulation and signs of cerebral palsy) with few having a somewhat milder impairment. 12 (of the 14) presented with epilepsy (spasms, myoclonic seizures, focal seizures with/without generalization or generalized tonic-clonic seizures) with onset most often in early infancy. Upon brain MRI (in 12 individuals), 5 presented polymicrogyria, 2 others pachygyria, 4 with brain atrophy, etc. All individuals were found to harbor biallelic TMX2 mutations by exome sequencing while previous investigations in several had ruled out alternative causes (infections, metabolic or chromosomal anomalies). Missense variants, an in-frame deletion as well as pLoF (stopgain/frameshift) variants were reported. [NM_015959.3 used as ref below]. The effect of variants was supported by mRNA studies, eg. RT-qPCR/allele specific RT-qPCR. The latter proved reduced expression for a frameshift variant (c.391dup / p.Leu131Profs6) most likely due to NMD. Total mRNA levels were also 23% lower in an individual compound htz for a missense variant and a stopgain one localized in the last exon (c.757C>T / p.Arg253). As for the previously reported c.614G>A (p.Arg205Gln), affecting the last nucleotide of exon 6, total mRNA in skin fibroblasts from a homozygous individual was not significantly decreased. RNA-Seq however demonstrated the presence of 4 different transcripts (roughly 25% each), one representing the regular mRNA, one with intron 6 retention (also present at low levels in healthy individuals), one with loss of 11 nucleotides within exon 6 and a fourth one due to in-frame skipping of exon 6. *To the best of my understanding : Thioredoxin (TRX)-related transmembrane proteins (TMX) belong to the broader family of oxidoreductases of protein disulfide isomerase (PDI) having an important role in protein folding. Study of the data from the Allen Human Brain Atlas suggest relevant fetal expression also increasing during postnatal life. As RNA-seq was carried out for 2 individuals, GO analysis suggested that the most deregulated clusters of genes are implicated in post-translational protein modifications (as would be expected for PDIs), membranes and synapse while pathway analysis suggested that relevant categories were inhibited eg. nervous system development/function and cell growth/proliferation/survival. Upon transfection of HEK293T cells, exogenous TMX2 was shown to co-localize with calnexin (CNX) to the (ER) mitochondria-associated-membrane. Mass-spectrometry based analysis of co-immunoprecipitated proteins confirmed interaction with CNX but also other regulators of calcium homeostasis, mitochondrial membrane components and respiratory chain NADH dehydrogenase. Study of the mitochondrial activity of TMX2-deficient fibroblasts suggested reduced respiratory reserve capacity, compensated by increased glycolytic activity. TMX2 occurs in both reduced and oxidized monomeric form. It also forms (homo)dimers with the ratio of dimers/monomers increasing under conditions of oxidative stress. Variant TMX2 increased propensity to form dimers, thus mimicking increased oxidative state. This was observed under stress but also under native conditions. --------- Created: 26 Nov 2019, 11:21 p.m. \| Last Modified: 26 Nov 2019, 11:21 p.m. Panel Version: 2.1122 [Previous review] PMID: 31586943 - Ghosh et al. 2019 - reported on 8 individuals from 4 consanguineous families from the Middle East and Central Asia, all with a phenotype of DD/ID, seizures and microcephaly with lissencephaly (microlissencephaly is the term applying to the combination of two) upon brain MRI. All patients were investigated by exome sequencing and the variant localized within a region of ROH which was common to all 4 families. All were homozygous for a TMX2 missense variant (NM_001144012.2:c.500G>A or p.Arg167Gln / NM_015959.4:c.614G>A p.Arg205Gln or hg38 - Chr11:g.57739039G>A). The variant was considered to be the best candidate, upon review of all other homozygous ones. Sanger sequencing confirmed homozygosity for the variant in affected subjects, with additional compatible segregation studies including parents in all families as well as unaffected sibs (in two families). Despite presence of the same mutation in all, several proximal to this variant SNPs did not appear to be shared among the families studied, thus suggesting that the variant had arisen within different haplotype blocks. The authors comment that the variant was not previously identified in public databases. (The variant seems to correspond to rs370455806, present in 10 htz individuals in gnomAD, as well as in the GME database [GME Genotype Count 992:0:1 (hmz?) \| Allele Count: 2,1984] . GME includes primarily - although not necessarily - healthy individuals). This SNV affecting the last nucleotide of an exon of several transcripts (correct ref. is NM_001144012.2 as appears in the supplement / using NM_001347898.1 as in the fig./text the variant would lie within an intron), an eventual splicing effect was studied. mRNA transcript levels were assessed following RT-PCR using different sets of primers. There was no evidence of novel splice isoforms but mRNA levels were reduced compared to controls (15-50% in affected individuals, to a lesser level in carriers). This led to the hypothesis that NMD of an aberrantly spliced mRNA might apply, although this was not proven. TMX2 encodes a protein disulfide isomerase (PDI). PDIs are transmembrane ER proteins which have a critical role in protein folding (PMID cited: 12670024). There were no relevant studies carried out in the article. As for animal models, the authors comment that mice homozygous for null mutations display preweaning lethality with complete penetrance.(http://www.informatics.jax.org/diseasePortal/popup?isPhenotype=true&markerID=MGI:1914208&header=mortality/aging). ------- Previously, Schot el al. (ESHG Conference 2018 Oral Presentation - Mutations in the thioredoxin related gene TMX2 cause primary microcephaly, polymicrogyria and severe neurodegeneration with impaired mitochondrial energy metabolism - available in PMID: 31270415 / https://www.nature.com/articles/s41431-019-0407-4 ) reported on 7 individuals from 5 unrelated families with biallelic TMX2 mutations. A newborn with microcephaly, polymicrogyria who died of refractory epilepsy, was compound heterozygous for 2 TMX2 variants. 6 additional individuals (from 4 unrelated families) with similar phenotype were found to harbor biallelic TMX2 mutations. It was commented that TMX2 is enriched in mitochondria-associated membrane of the ER with a role in ER stress protection and regulation of neuronal apoptosis. In line with this, fibroblasts from 2 unrelated patients showed secondary OXPHOS deficiency and increased glycolytic activity (the latter possibly as a compensatory mechanism). ------- There is no associated phenotype in OMIM/G2P/SysID. ------- Overall this gene could be considered for inclusion in the ID/epilepsy panel probably with amber (/red) rating pending further evidence. Sources: Literature Sources: Literature
26 Nov 2019	Early onset or syndromic epilepsy v1.475	IDH2	Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green.Refers to glioma patients: not a seizure disorder. Demoted from Green to RED.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Refers to glioma patients- not a seizure disorder. Demoted from Green to RED.
26 Nov 2019	Early onset or syndromic epilepsy v1.475	CYP27A1	Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. prominent phenotype is dystonia/ataxia. Demoted from Green to Amber.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Prominent phenotype is dystonia/ataxia. Demoted from Green to Amber.
26 Nov 2019	Early onset or syndromic epilepsy v1.475	SCN9A	Rebecca Foulger Publications for gene: SCN9A were set to 19763161; 29500686
26 Nov 2019	Early onset or syndromic epilepsy v1.474	FLNA	Rebecca Foulger changed review comment from: Comment on mode of inheritance: At the Webex call 22nd November 2019, it was notes that want to target FEMALES ONLY for the Heterotopia periventricular phenotype.; to: Comment on mode of inheritance: At the Webex call 22nd November 2019, it was noted that want to target FEMALES ONLY for the Heterotopia periventricular phenotype.
26 Nov 2019	Early onset or syndromic epilepsy v1.474	PEX6	Rebecca Foulger Classified gene: PEX6 as Amber List (moderate evidence)
26 Nov 2019	Early onset or syndromic epilepsy v1.474	PEX6	Rebecca Foulger Gene: pex6 has been classified as Amber List (Moderate Evidence).
26 Nov 2019	Early onset or syndromic epilepsy v1.473	PEX6	Rebecca Foulger commented on gene: PEX6: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that PEX genes are better tested through the metabolic panel, and should be demoted to Amber.
26 Nov 2019	Early onset or syndromic epilepsy v1.473	PEX3	Rebecca Foulger Classified gene: PEX3 as Amber List (moderate evidence)
26 Nov 2019	Early onset or syndromic epilepsy v1.473	PEX3	Rebecca Foulger Gene: pex3 has been classified as Amber List (Moderate Evidence).
26 Nov 2019	Early onset or syndromic epilepsy v1.472	PEX3	Rebecca Foulger commented on gene: PEX3: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that PEX genes are better tested through the metabolic panel, and should be demoted to Amber.
26 Nov 2019	Early onset or syndromic epilepsy v1.472	PEX2	Rebecca Foulger Classified gene: PEX2 as Amber List (moderate evidence)
26 Nov 2019	Early onset or syndromic epilepsy v1.472	PEX2	Rebecca Foulger Gene: pex2 has been classified as Amber List (Moderate Evidence).
26 Nov 2019	Early onset or syndromic epilepsy v1.471	PEX2	Rebecca Foulger commented on gene: PEX2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that PEX genes are better tested through the metabolic panel, and should be demoted to Amber.
26 Nov 2019	Early onset or syndromic epilepsy v1.471	PEX19	Rebecca Foulger Classified gene: PEX19 as Amber List (moderate evidence)
26 Nov 2019	Early onset or syndromic epilepsy v1.471	PEX19	Rebecca Foulger Gene: pex19 has been classified as Amber List (Moderate Evidence).
26 Nov 2019	Early onset or syndromic epilepsy v1.470	PEX19	Rebecca Foulger commented on gene: PEX19: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that PEX genes are better tested through the metabolic panel, and should be demoted to Amber.
26 Nov 2019	Early onset or syndromic epilepsy v1.470	PEX13	Rebecca Foulger Classified gene: PEX13 as Amber List (moderate evidence)
26 Nov 2019	Early onset or syndromic epilepsy v1.470	PEX13	Rebecca Foulger Gene: pex13 has been classified as Amber List (Moderate Evidence).
26 Nov 2019	Early onset or syndromic epilepsy v1.469	PEX13	Rebecca Foulger commented on gene: PEX13: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that PEX genes are better tested through the metabolic panel, and should be demoted to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.469	BSCL2	Rebecca Foulger Added comment: Comment on mode of inheritance: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that MOI should change from 'BOTH monoallelic and biallelic' to 'BIALLELIC': just one monoallelic case so far, which could be a false positive.
25 Nov 2019	Early onset or syndromic epilepsy v1.469	BSCL2	Rebecca Foulger Mode of inheritance for gene: BSCL2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
25 Nov 2019	Early onset or syndromic epilepsy v1.468	NDUFA1	Rebecca Foulger Added comment: Comment on mode of inheritance: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that MOI should be updated from XLR to XLD.
25 Nov 2019	Early onset or syndromic epilepsy v1.468	NDUFA1	Rebecca Foulger Mode of inheritance for gene: NDUFA1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
25 Nov 2019	Early onset or syndromic epilepsy v1.467	NSDHL	Rebecca Foulger Added comment: Comment on mode of inheritance: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that MOI should remain as XLR.
25 Nov 2019	Early onset or syndromic epilepsy v1.467	NSDHL	Rebecca Foulger Mode of inheritance for gene: NSDHL was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
25 Nov 2019	Early onset or syndromic epilepsy v1.466	ADAR	Rebecca Foulger Added comment: Comment on mode of inheritance: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that MOI should remain as BIALLELIC: No current evidence for seizures in monoallelic cases.
25 Nov 2019	Early onset or syndromic epilepsy v1.466	ADAR	Rebecca Foulger Mode of inheritance for gene: ADAR was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
25 Nov 2019	Early onset or syndromic epilepsy v1.465	DNAJC5	Rebecca Foulger Classified gene: DNAJC5 as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.465	DNAJC5	Rebecca Foulger Gene: dnajc5 has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.464	DNAJC5	Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Demoted from Green to Amber.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Seizures present later. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.464	DNAJC5	Rebecca Foulger commented on gene: DNAJC5: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.464	SGSH	Rebecca Foulger commented on gene: SGSH: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Kept rating as Green.
25 Nov 2019	Early onset or syndromic epilepsy v1.464	EXT2	Rebecca Foulger Classified gene: EXT2 as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.464	EXT2	Rebecca Foulger Gene: ext2 has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.463	EXT2	Rebecca Foulger commented on gene: EXT2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Seizures not a presenting feature. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.463	CLPB	Rebecca Foulger Classified gene: CLPB as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.463	CLPB	Rebecca Foulger Gene: clpb has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.462	CLPB	Rebecca Foulger commented on gene: CLPB: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Although there are three cases, most patients don't have seizures. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.462	TMEM70	Rebecca Foulger Classified gene: TMEM70 as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.462	TMEM70	Rebecca Foulger Gene: tmem70 has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.461	TMEM70	Rebecca Foulger commented on gene: TMEM70: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Insufficient seizure evidence. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.461	SLC6A19	Rebecca Foulger Classified gene: SLC6A19 as Red List (low evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.461	SLC6A19	Rebecca Foulger Gene: slc6a19 has been classified as Red List (Low Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.460	SLC6A19	Rebecca Foulger commented on gene: SLC6A19: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Epilepsy is not a key feature. Demoted from Green to Red.
25 Nov 2019	Early onset or syndromic epilepsy v1.460	SLC35A1	Rebecca Foulger Publications for gene: SLC35A1 were set to 23873973; 15576474; 28856833; 30115659
25 Nov 2019	Early onset or syndromic epilepsy v1.459	SLC35A1	Rebecca Foulger Classified gene: SLC35A1 as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.459	SLC35A1	Rebecca Foulger Gene: slc35a1 has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.458	SLC35A1	Rebecca Foulger commented on gene: SLC35A1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.458	SCO2	Rebecca Foulger Publications for gene: SCO2 were set to 10545952; 10749987; 18924171
25 Nov 2019	Early onset or syndromic epilepsy v1.457	SCO2	Rebecca Foulger Classified gene: SCO2 as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.457	SCO2	Rebecca Foulger Gene: sco2 has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.456	SCO2	Rebecca Foulger commented on gene: SCO2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.456	SCO1	Rebecca Foulger Classified gene: SCO1 as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.456	SCO1	Rebecca Foulger Gene: sco1 has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.455	SCO1	Rebecca Foulger commented on gene: SCO1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.455	QDPR	Rebecca Foulger Classified gene: QDPR as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.455	QDPR	Rebecca Foulger Gene: qdpr has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.454	QDPR	Rebecca Foulger commented on gene: QDPR: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.454	PRODH	Rebecca Foulger Classified gene: PRODH as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.454	PRODH	Rebecca Foulger Gene: prodh has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.453	PRODH	Rebecca Foulger commented on gene: PRODH: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.453	PEX7	Rebecca Foulger Classified gene: PEX7 as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.453	PEX7	Rebecca Foulger Gene: pex7 has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.452	PEX7	Rebecca Foulger commented on gene: PEX7: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.452	PEX12	Rebecca Foulger Classified gene: PEX12 as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.452	PEX12	Rebecca Foulger Gene: pex12 has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.451	PEX12	Rebecca Foulger commented on gene: PEX12: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted all PEX genes from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.451	PEX10	Rebecca Foulger Publications for gene: PEX10 were set to 20695019
25 Nov 2019	Early onset or syndromic epilepsy v1.450	PEX10	Rebecca Foulger Classified gene: PEX10 as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.450	PEX10	Rebecca Foulger Gene: pex10 has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.449	PEX10	Rebecca Foulger commented on gene: PEX10: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted all PEX genes from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.449	PEX1	Rebecca Foulger Classified gene: PEX1 as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.449	PEX1	Rebecca Foulger Gene: pex1 has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.448	PEX1	Rebecca Foulger commented on gene: PEX1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted all PEX genes from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.448	MTR	Rebecca Foulger Classified gene: MTR as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.448	MTR	Rebecca Foulger Gene: mtr has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.447	MTR	Rebecca Foulger commented on gene: MTR: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Metabolic phenotype with failure to thrive, with seizures presenting later. Better tested through the metabolic panel. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.447	IDH2	Rebecca Foulger Classified gene: IDH2 as Red List (low evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.447	IDH2	Rebecca Foulger Gene: idh2 has been classified as Red List (Low Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.446	IDH2	Rebecca Foulger commented on gene: IDH2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green.Refers to glioma patients: not a seizure disorder. Demoted from Green to RED.
25 Nov 2019	Early onset or syndromic epilepsy v1.446	HLCS	Rebecca Foulger Classified gene: HLCS as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.446	HLCS	Rebecca Foulger Gene: hlcs has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.445	HLCS	Rebecca Foulger commented on gene: HLCS: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.445	GSS	Rebecca Foulger Classified gene: GSS as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.445	GSS	Rebecca Foulger Gene: gss has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.444	GSS	Rebecca Foulger commented on gene: GSS: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.444	GLYCTK	Rebecca Foulger Classified gene: GLYCTK as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.444	GLYCTK	Rebecca Foulger Gene: glyctk has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.443	GLYCTK	Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Bordeline cases from literature, variable phenotype and needs better genotype:phenotype correlation. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.443	GLYCTK	Rebecca Foulger commented on gene: GLYCTK: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.443	GFM1	Rebecca Foulger Classified gene: GFM1 as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.443	GFM1	Rebecca Foulger Gene: gfm1 has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.442	GFM1	Rebecca Foulger commented on gene: GFM1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.442	GCH1	Rebecca Foulger Classified gene: GCH1 as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.442	GCH1	Rebecca Foulger Gene: gch1 has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.441	GCH1	Rebecca Foulger commented on gene: GCH1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.441	FH	Rebecca Foulger Classified gene: FH as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.441	FH	Rebecca Foulger Gene: fh has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.440	FH	Rebecca Foulger commented on gene: FH: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.440	FAR1	Rebecca Foulger Classified gene: FAR1 as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.440	FAR1	Rebecca Foulger Gene: far1 has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.439	FAR1	Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Borderline evidence and variable phenotype. Requires better genotype:phenotype correlation. Demoted from Green to Amber.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.439	FAR1	Rebecca Foulger commented on gene: FAR1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Borderline evidence and variable phenotype. Requires better genotype:phenotype correlation. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.439	DOLK	Rebecca Foulger Classified gene: DOLK as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.439	DOLK	Rebecca Foulger Gene: dolk has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.438	DOLK	Rebecca Foulger commented on gene: DOLK: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.438	CYP27A1	Rebecca Foulger Classified gene: CYP27A1 as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.438	CYP27A1	Rebecca Foulger Gene: cyp27a1 has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.437	CYP27A1	Rebecca Foulger commented on gene: CYP27A1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. prominent phenotype is dystonia/ataxia. Demoted from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.437	PTS	Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Seizures may present before 9 months, and could be the primary presentation in these cases. Promoted from Amber to Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Seizures may present before 9 months, and could be the primary presentation in these cases. Since the last group review, PTS has also been promoted to Green on the 'Inborn errors of metabolism' panel (v 1.407). Promoted PTS from Amber to Green on the epilepsy panel.
25 Nov 2019	Early onset or syndromic epilepsy v1.437	PTS	Rebecca Foulger Classified gene: PTS as Green List (high evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.437	PTS	Rebecca Foulger Gene: pts has been classified as Green List (High Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.436	PTS	Rebecca Foulger commented on gene: PTS: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Seizures may present before 9 months, and could be the primary presentation in these cases. Promoted from Amber to Green.
25 Nov 2019	Early onset or syndromic epilepsy v1.436	RRM2B	Rebecca Foulger commented on gene: RRM2B: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Kept rating as Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.436	PEX5	Rebecca Foulger commented on gene: PEX5: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Kept rating as Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.436	GTPBP3	Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Kept rating as Amber.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Kept rating as Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.436	GTPBP3	Rebecca Foulger commented on gene: GTPBP3: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Kept rating as Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.436	DPM2	Rebecca Foulger commented on gene: DPM2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Kept rating as Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.436	SCN9A	Rebecca Foulger Classified gene: SCN9A as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.436	SCN9A	Rebecca Foulger Gene: scn9a has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.435	SCN9A	Rebecca Foulger commented on gene: SCN9A: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Demoted SCN9A from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.435	KCNA1	Rebecca Foulger Classified gene: KCNA1 as Amber List (moderate evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.435	KCNA1	Rebecca Foulger Gene: kcna1 has been classified as Amber List (Moderate Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.434	KCNA1	Rebecca Foulger commented on gene: KCNA1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Demoted KCNA1 from Green to Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.434	FLNA	Rebecca Foulger Added comment: Comment on mode of inheritance: At the Webex call 22nd November 2019, it was notes that want to target FEMALES ONLY for the Heterotopia periventricular phenotype.
25 Nov 2019	Early onset or syndromic epilepsy v1.434	FLNA	Rebecca Foulger Mode of inheritance for gene: FLNA was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
25 Nov 2019	Early onset or syndromic epilepsy v1.433	FLNA	Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Kept rating of FLNA as Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy, and following Green ratings by Alisdair McNeill and Alison Callaway: Agreed that there is enough evidence to rate this gene Green. Kept rating of FLNA as Green.
25 Nov 2019	Early onset or syndromic epilepsy v1.433	FLNA	Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Kept rating as Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Kept rating of FLNA as Green.
25 Nov 2019	Early onset or syndromic epilepsy v1.433	FLNA	Rebecca Foulger commented on gene: FLNA: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Kept rating as Green.
25 Nov 2019	Early onset or syndromic epilepsy v1.433	CACNA2D2	Rebecca Foulger Phenotypes for gene: CACNA2D2 were changed from Absence epilepsy to Absence epilepsy; Cerebellar atrophy with seizures and variable developmental delay, 618501
25 Nov 2019	Early onset or syndromic epilepsy v1.432	CACNA2D2	Rebecca Foulger Classified gene: CACNA2D2 as Green List (high evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.432	CACNA2D2	Rebecca Foulger Gene: cacna2d2 has been classified as Green List (High Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.431	CACNA2D2	Rebecca Foulger commented on gene: CACNA2D2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Promoted from Amber to Green.
25 Nov 2019	Early onset or syndromic epilepsy v1.431	ALG8	Rebecca Foulger commented on gene: ALG8: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Although there is inconsistency amongst patients, there are sufficient cases for a Green rating. Kept rating as Green.
25 Nov 2019	Early onset or syndromic epilepsy v1.431	TDP2	Rebecca Foulger commented on gene: TDP2
25 Nov 2019	Early onset or syndromic epilepsy v1.431	GOT2	Rebecca Foulger Classified gene: GOT2 as Green List (high evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.431	GOT2	Rebecca Foulger Gene: got2 has been classified as Green List (High Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.430	GOT2	Rebecca Foulger commented on gene: GOT2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Promoted from Amber to Green.
25 Nov 2019	Early onset or syndromic epilepsy v1.430	HNRNPR	Rebecca Foulger Mode of inheritance for gene: HNRNPR was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
25 Nov 2019	Early onset or syndromic epilepsy v1.429	HNRNPR	Rebecca Foulger Classified gene: HNRNPR as Green List (high evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.429	HNRNPR	Rebecca Foulger Gene: hnrnpr has been classified as Green List (High Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.428	HNRNPR	Rebecca Foulger commented on gene: HNRNPR: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Although obvious dysmoprhism is associated with the phenotype, it meets the criteria for a Green rating. Promoted from Amber to Green.
25 Nov 2019	Early onset or syndromic epilepsy v1.428	ZNF142	Rebecca Foulger Classified gene: ZNF142 as Green List (high evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.428	ZNF142	Rebecca Foulger Gene: znf142 has been classified as Green List (High Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.427	ZNF142	Rebecca Foulger commented on gene: ZNF142: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Sufficient cases for inclusion. Promoted from Amber to Green.
25 Nov 2019	Early onset or syndromic epilepsy v1.427	TRRAP	Rebecca Foulger commented on gene: TRRAP: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Seizures aren't a prominent feature. Kept rating as Amber.
25 Nov 2019	Early onset or syndromic epilepsy v1.427	NPRL2	Rebecca Foulger Classified gene: NPRL2 as Green List (high evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.427	NPRL2	Rebecca Foulger Gene: nprl2 has been classified as Green List (High Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.426	NPRL2	Rebecca Foulger commented on gene: NPRL2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Sufficient cases to support gene:disease association, although unaffected carriers/incomplete penetrance may make variant interpretation difficult. Promoted from Amber to Green with the option to review on subsequent versions.
25 Nov 2019	Early onset or syndromic epilepsy v1.426	HCN2	Rebecca Foulger Marked gene: HCN2 as ready
25 Nov 2019	Early onset or syndromic epilepsy v1.426	HCN2	Rebecca Foulger Gene: hcn2 has been classified as Green List (High Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.426	HCN2	Rebecca Foulger commented on gene: HCN2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Although this is a borderline case with questions over phenotype segregation, there are sufficient cases to support inclusion. Although seizures aren’t one of the cardinal phenotypes, most cases will be trios and therefore there will be less issues in being inclusive. Kept rating of HCN2 as Green with the option of review on subsequent panel versions.
25 Nov 2019	Early onset or syndromic epilepsy v1.426	AFF3	Rebecca Foulger Classified gene: AFF3 as Green List (high evidence)
25 Nov 2019	Early onset or syndromic epilepsy v1.426	AFF3	Rebecca Foulger Gene: aff3 has been classified as Green List (High Evidence).
25 Nov 2019	Early onset or syndromic epilepsy v1.425	AFF3	Rebecca Foulger commented on gene: AFF3: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green: Sufficient evidence in pre-print Voisin et al., 2019 article. Promoted AFF3 from Amber to Green.
22 Nov 2019	Early onset or syndromic epilepsy v1.425	SCN9A	Alison Callaway reviewed gene: SCN9A: Rating: AMBER; Mode of pathogenicity: None; Publications: 30834459, 29500686; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
22 Nov 2019	Early onset or syndromic epilepsy v1.425	ALG8	Rebecca Foulger changed review comment from: 26066342 (Hock et al., 2015) describe 3 new patients with ALG8-CDG, provide an update on 2 previous patients and summarise 10 previous patients. The 15 patients total included 4 pairs of siblings. Brain involvement (psychomotor disability or seizures or ataxia or structural anomalies) were seen in 12/13 patients.; to: 26066342 (Hock et al., 2015) describe 3 new patients with ALG8-CDG, provide an update on 2 previous patients and summarise 10 previous patients. The 15 patients total included 4 pairs of siblings. Brain involvement (psychomotor disability or seizures or ataxia or structural anomalies) was seen in 12/13 patients.
22 Nov 2019	Early onset or syndromic epilepsy v1.425	DMXL2	Konstantinos Varvagiannis changed review comment from: This gene can be considered for inclusion in both ID and epilepsy panels probably with green (ID and epilepsy with >=4 relevant individuals/families/variants and >=2 studies, role of the protein, effect of variants in most cases demonstrated, phenotypic similarities with other disorders affecting autophagy, some evidence from animal models, etc) or amber rating. Rare heterozygous variants disrupting DMXL2 (intragenic losses/gains, SNVs, CNVs affecting also additional genes) have been reported in individuals with variable neurodevelopmental disorders (ASD and ID) or psychiatric phenotypes [Costain et al. 2019 - PMID: 30732576 - summarized in Table 1]. (Highly) variable expressivity and possibly incomplete penetrance were proposed in the respective study. As a result evidence for ID/seizures due to monoallelic variants appears to be relatively limited. DD, ID and (probably) epilepsy appear however to be constant features in several individuals with biallelic pathogenic variants as summarized in the studies below. OMIM recently added a relevant entry with the DMXL2-associated phenotypes being the following: - Epileptic encephalopathy, early infantile, 81; EIEE81 - 618663 (AD) [based on refs 2,3] - ?Deafness, autosomal dominant 71 - 617605 (AD) [DD/ID/seizures are not part of the phenotype] - ?Polyendocrine-polyneuropathy syndrome - 616113 (AR) [based on ref1] DMXL2 is not associated with any phenotype in G2P. In SysID it is listed as a candidate ID gene based on the report by Tata et al (ref1). This gene is included in some gene panels for ID. [1] Tata el al. (2014 - PMID: 25248098) reported on 3 sibs born to consanguineous Senegalese parents, presenting with a progressive endocrine and neurodevelopmental disorder. Features incl. incomplete puberty, central hypothyroidism, abnormal glucose regulation, moderate ID (3/3) and peripheral polyneuropathy. Seizures were not part of the phenotype. Linkage analysis suggested 2 candidate regions on chromosomes 13 and 15 with a LOD score of 2.5. High throughput sequencing of genes within these regions (~500) in an affected member and parent revealed a 15 bp in-frame deletion of DMXL2 (NM_015263.4:c.5827_5841del / p.Asp1943_Ser1947del). Sanger sequencing of other affected and unaffected members supported AR inheritance. RT-qPCR demonstrated that DMXL2 mRNA levels in blood lymphocytes were significantly lower in homozygous patients compared to heterozygous or wt family members or controls. The authors demonstrated that the encoded protein (rabconnectin-3a) is a synaptic protein (expressed in exocytosis vesicles) at the ends of axons of GnRH producing neurons. Neuron-specific deletion of one allele in mice resulted in delayed puberty and very low fertility. Adult mice had lower number of GnRH neurons in hypothalamus. siRNA-mediated downregulation of Dmxl2 expression in an insulin-secreting cell line resulted in only slight insulin secretion in response to augmenting concentrations of glucose, providing evidence of involvement of the protein in control of regulated insulin secretion. ----------- [2] Maddirevula et al. (2019 - PMID: 30237576) reported briefly on a 36 months old boy, born to consanguineous parents, homozygous for a frameshift DMXL2 variant [individual 17-3220 \| NM_001174117.1:c.4349_4350insTTACATGA or p.(Glu1450Aspfs23)]. Features included focal seizures (onset at the age of 3m) with subsequent global DD, absent eye contact, cerebral atrophy and macrocephaly. This individual was identified following re-evaluation of exome data in a database of ~1550 exomes specifically for homozygous variants that would have been classified earlier as LP/P if the respective gene had sufficient evidence for association with a disorder. The family was not reported to have other affected members. As the authors noted, the boy was not known to have the multi-endocrine abnormalities reported by Tata et al. There are no additional information provided (eg. on confirmation of variants, etc). ----------- [3] Esposito et al. (2019 - PMID: 31688942) report on 3 sibling pairs (all 3 families unrelated) with biallelic DMXL2 mutations and summarize previous evidence on the gene and the DMXL2-related phenotypes. All presented a highly similar phenotype of Ohtahara syndrome (seizures with onset in the first days of life, tonic/myoclonic/occasionaly focal, burst-suppression upon EEG), profound DD/ID, quadriparesis, sensorineural hearing loss and presence of dysmorphic features. Sibs from 2 families presented evidence of peripheral polyneuropathy. Early brain MRIs revealed thin CC and hypomyelination in all, with later scans suggestive of gray and white matter shrinkage with leukoencephalopathy. None achieved developmental skills following birth with 5/6 deceased by the age of 9 years. Exome sequencing revealed biallelic DMXL2 variants in all, with compatible parental segregation studies (NM_015263.3): - Fam1 (2 sibs) : c.5135C>T (p.Ala1712Val) in trans with c.4478C>G (p.Ser1493) - Fam2 (2 sibs) : homozygosity for c.4478C>A (p.Ser1493) - Fam3 (2 sibs) : homozygosity for c.7518-1G>A Heterozygous parents (aged 39-59) did not exhibit hearing impairment [report of a single multigenerational family by Chen et al (2017 - PMID: 27657680) where a heterozygous missense variant segregated with hearing loss - respective OMIM entry: ?Deafness, autosomal dominant 71 - 617605]. In patients' fibroblasts, effect of the variants on mRNA/protein expression was demonstrated with mRNA expressed only in a patient from family 1, and degraded/absent for the 2 stopgain SNVs affecting codon 1493. Skipping of ex31 leading to frameshift/introduction of a PTC was shown for the splice variant (p.Trp2508Argfs4 secondary to c.7518-1G>A). Protein was also absent upon western-blot. DMXL2 encodes a vesicular protein, DmX-Like protein 2 or rabconnectin-3a (cited Tata et al). The gene is expressed in brain ( https://www.gtexportal.org/home/gene/DMXL2 ). As Esposito et al comment, it is known to regulate the trafficking and activity of v-ATPase the latter having a role in acidifying intracellular organelles and promoting endosomal maturation (cited PMIDs : 25248098, 19758563, 22875945, 24802872). In line with this, staining of patients' fibroblasts using the acidotropic dye LysoTracker demonstrated increased signal, reversed by re-expression of DMXL2 protein. Overall an acidic shift in pH with impairment of lysosomal structures and function was suggested. The authors provided additional evidence for altered lysosomal function and associated autophagy with accumulation of autophagy receptors (eg p62) and substrates (polyubiquitinated proteins). Vacuolization and accumulation of atypical fusion-like structures was shown upon ultrastractural analysis. shRNA-mediated downregulation/silencing of Dmxl2 in mouse hippocampal neurons resulted also in altered lysosomal structures and defective autophagy. The neurons exhibited impaired neurite elongation and synapse formation. The authors suggest similarities with Vici syndrome, where biallelic EPG5 mutations result in autophagic defects and clinical manifestations of DD/ID/epilepsy. Dmxl2 homozygous ko mice display embryonic lethality with heterozygous mice displaying macrocephaly and corpus callosum dysplasia (cited PMIDs: 25248098, 30735494) . Sources: Literature; to: This gene can be considered for inclusion in both ID and epilepsy panels probably with green (ID and epilepsy with >=4 relevant individuals/families/variants and >=2 studies, role of the protein, effect of variants in most cases demonstrated, phenotypic similarities with other disorders affecting autophagy, some evidence from animal models, etc) or amber rating. Rare heterozygous variants disrupting DMXL2 (intragenic losses/gains, SNVs, CNVs affecting also additional genes) have been reported in individuals with variable neurodevelopmental disorders (ASD and ID) or psychiatric phenotypes [Costain et al. 2019 - PMID: 30732576 - summarized in Table 1]. (Highly) variable expressivity and possibly incomplete penetrance were proposed in the respective study. As a result evidence for ID/seizures due to monoallelic variants appears to be relatively limited. DD, ID and (probably) epilepsy appear however to be constant features in several individuals with biallelic pathogenic variants as summarized in the studies below. OMIM recently added a relevant entry with the DMXL2-associated phenotypes being the following: - Epileptic encephalopathy, early infantile, 81; EIEE81 - 618663 (AR) [based on refs 2,3] - ?Deafness, autosomal dominant 71 - 617605 (AD) [DD/ID/seizures are not part of the phenotype] - ?Polyendocrine-polyneuropathy syndrome - 616113 (AR) [based on ref1] DMXL2 is not associated with any phenotype in G2P. In SysID it is listed as a candidate ID gene based on the report by Tata et al (ref1). This gene is included in some gene panels for ID. [1] Tata el al. (2014 - PMID: 25248098) reported on 3 sibs born to consanguineous Senegalese parents, presenting with a progressive endocrine and neurodevelopmental disorder. Features incl. incomplete puberty, central hypothyroidism, abnormal glucose regulation, moderate ID (3/3) and peripheral polyneuropathy. Seizures were not part of the phenotype. Linkage analysis suggested 2 candidate regions on chromosomes 13 and 15 with a LOD score of 2.5. High throughput sequencing of genes within these regions (~500) in an affected member and parent revealed a 15 bp in-frame deletion of DMXL2 (NM_015263.4:c.5827_5841del / p.Asp1943_Ser1947del). Sanger sequencing of other affected and unaffected members supported AR inheritance. RT-qPCR demonstrated that DMXL2 mRNA levels in blood lymphocytes were significantly lower in homozygous patients compared to heterozygous or wt family members or controls. The authors demonstrated that the encoded protein (rabconnectin-3a) is a synaptic protein (expressed in exocytosis vesicles) at the ends of axons of GnRH producing neurons. Neuron-specific deletion of one allele in mice resulted in delayed puberty and very low fertility. Adult mice had lower number of GnRH neurons in hypothalamus. siRNA-mediated downregulation of Dmxl2 expression in an insulin-secreting cell line resulted in only slight insulin secretion in response to augmenting concentrations of glucose, providing evidence of involvement of the protein in control of regulated insulin secretion. ----------- [2] Maddirevula et al. (2019 - PMID: 30237576) reported briefly on a 36 months old boy, born to consanguineous parents, homozygous for a frameshift DMXL2 variant [individual 17-3220 \| NM_001174117.1:c.4349_4350insTTACATGA or p.(Glu1450Aspfs23)]. Features included focal seizures (onset at the age of 3m) with subsequent global DD, absent eye contact, cerebral atrophy and macrocephaly. This individual was identified following re-evaluation of exome data in a database of ~1550 exomes specifically for homozygous variants that would have been classified earlier as LP/P if the respective gene had sufficient evidence for association with a disorder. The family was not reported to have other affected members. As the authors noted, the boy was not known to have the multi-endocrine abnormalities reported by Tata et al. There are no additional information provided (eg. on confirmation of variants, etc). ----------- [3] Esposito et al. (2019 - PMID: 31688942) report on 3 sibling pairs (all 3 families unrelated) with biallelic DMXL2 mutations and summarize previous evidence on the gene and the DMXL2-related phenotypes. All presented a highly similar phenotype of Ohtahara syndrome (seizures with onset in the first days of life, tonic/myoclonic/occasionaly focal, burst-suppression upon EEG), profound DD/ID, quadriparesis, sensorineural hearing loss and presence of dysmorphic features. Sibs from 2 families presented evidence of peripheral polyneuropathy. Early brain MRIs revealed thin CC and hypomyelination in all, with later scans suggestive of gray and white matter shrinkage with leukoencephalopathy. None achieved developmental skills following birth with 5/6 deceased by the age of 9 years. Exome sequencing revealed biallelic DMXL2 variants in all, with compatible parental segregation studies (NM_015263.3): - Fam1 (2 sibs) : c.5135C>T (p.Ala1712Val) in trans with c.4478C>G (p.Ser1493) - Fam2 (2 sibs) : homozygosity for c.4478C>A (p.Ser1493) - Fam3 (2 sibs) : homozygosity for c.7518-1G>A Heterozygous parents (aged 39-59) did not exhibit hearing impairment [report of a single multigenerational family by Chen et al (2017 - PMID: 27657680) where a heterozygous missense variant segregated with hearing loss - respective OMIM entry: ?Deafness, autosomal dominant 71 - 617605]. In patients' fibroblasts, effect of the variants on mRNA/protein expression was demonstrated with mRNA expressed only in a patient from family 1, and degraded/absent for the 2 stopgain SNVs affecting codon 1493. Skipping of ex31 leading to frameshift/introduction of a PTC was shown for the splice variant (p.Trp2508Argfs4 secondary to c.7518-1G>A). Protein was also absent upon western-blot. DMXL2 encodes a vesicular protein, DmX-Like protein 2 or rabconnectin-3a (cited Tata et al). The gene is expressed in brain ( https://www.gtexportal.org/home/gene/DMXL2 ). As Esposito et al comment, it is known to regulate the trafficking and activity of v-ATPase the latter having a role in acidifying intracellular organelles and promoting endosomal maturation (cited PMIDs : 25248098, 19758563, 22875945, 24802872). In line with this, staining of patients' fibroblasts using the acidotropic dye LysoTracker demonstrated increased signal, reversed by re-expression of DMXL2 protein. Overall an acidic shift in pH with impairment of lysosomal structures and function was suggested. The authors provided additional evidence for altered lysosomal function and associated autophagy with accumulation of autophagy receptors (eg p62) and substrates (polyubiquitinated proteins). Vacuolization and accumulation of atypical fusion-like structures was shown upon ultrastractural analysis. shRNA-mediated downregulation/silencing of Dmxl2 in mouse hippocampal neurons resulted also in altered lysosomal structures and defective autophagy. The neurons exhibited impaired neurite elongation and synapse formation. The authors suggest similarities with Vici syndrome, where biallelic EPG5 mutations result in autophagic defects and clinical manifestations of DD/ID/epilepsy. Dmxl2 homozygous ko mice display embryonic lethality with heterozygous mice displaying macrocephaly and corpus callosum dysplasia (cited PMIDs: 25248098, 30735494) . Sources: Literature
22 Nov 2019	Early onset or syndromic epilepsy v1.425	DMXL2	Konstantinos Varvagiannis gene: DMXL2 was added gene: DMXL2 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: DMXL2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: DMXL2 were set to 25248098; 30237576; 31688942; 30732576 Phenotypes for gene: DMXL2 were set to Epileptic encephalopathy, early infantile, 81, MIM 618663; ?Polyendocrine-polyneuropathy syndrome, MIM 616113 Penetrance for gene: DMXL2 were set to unknown Review for gene: DMXL2 was set to GREEN Added comment: This gene can be considered for inclusion in both ID and epilepsy panels probably with green (ID and epilepsy with >=4 relevant individuals/families/variants and >=2 studies, role of the protein, effect of variants in most cases demonstrated, phenotypic similarities with other disorders affecting autophagy, some evidence from animal models, etc) or amber rating. Rare heterozygous variants disrupting DMXL2 (intragenic losses/gains, SNVs, CNVs affecting also additional genes) have been reported in individuals with variable neurodevelopmental disorders (ASD and ID) or psychiatric phenotypes [Costain et al. 2019 - PMID: 30732576 - summarized in Table 1]. (Highly) variable expressivity and possibly incomplete penetrance were proposed in the respective study. As a result evidence for ID/seizures due to monoallelic variants appears to be relatively limited. DD, ID and (probably) epilepsy appear however to be constant features in several individuals with biallelic pathogenic variants as summarized in the studies below. OMIM recently added a relevant entry with the DMXL2-associated phenotypes being the following: - Epileptic encephalopathy, early infantile, 81; EIEE81 - 618663 (AD) [based on refs 2,3] - ?Deafness, autosomal dominant 71 - 617605 (AD) [DD/ID/seizures are not part of the phenotype] - ?Polyendocrine-polyneuropathy syndrome - 616113 (AR) [based on ref1] DMXL2 is not associated with any phenotype in G2P. In SysID it is listed as a candidate ID gene based on the report by Tata et al (ref1). This gene is included in some gene panels for ID. [1] Tata el al. (2014 - PMID: 25248098) reported on 3 sibs born to consanguineous Senegalese parents, presenting with a progressive endocrine and neurodevelopmental disorder. Features incl. incomplete puberty, central hypothyroidism, abnormal glucose regulation, moderate ID (3/3) and peripheral polyneuropathy. Seizures were not part of the phenotype. Linkage analysis suggested 2 candidate regions on chromosomes 13 and 15 with a LOD score of 2.5. High throughput sequencing of genes within these regions (~500) in an affected member and parent revealed a 15 bp in-frame deletion of DMXL2 (NM_015263.4:c.5827_5841del / p.Asp1943_Ser1947del). Sanger sequencing of other affected and unaffected members supported AR inheritance. RT-qPCR demonstrated that DMXL2 mRNA levels in blood lymphocytes were significantly lower in homozygous patients compared to heterozygous or wt family members or controls. The authors demonstrated that the encoded protein (rabconnectin-3a) is a synaptic protein (expressed in exocytosis vesicles) at the ends of axons of GnRH producing neurons. Neuron-specific deletion of one allele in mice resulted in delayed puberty and very low fertility. Adult mice had lower number of GnRH neurons in hypothalamus. siRNA-mediated downregulation of Dmxl2 expression in an insulin-secreting cell line resulted in only slight insulin secretion in response to augmenting concentrations of glucose, providing evidence of involvement of the protein in control of regulated insulin secretion. ----------- [2] Maddirevula et al. (2019 - PMID: 30237576) reported briefly on a 36 months old boy, born to consanguineous parents, homozygous for a frameshift DMXL2 variant [individual 17-3220 \| NM_001174117.1:c.4349_4350insTTACATGA or p.(Glu1450Aspfs23)]. Features included focal seizures (onset at the age of 3m) with subsequent global DD, absent eye contact, cerebral atrophy and macrocephaly. This individual was identified following re-evaluation of exome data in a database of ~1550 exomes specifically for homozygous variants that would have been classified earlier as LP/P if the respective gene had sufficient evidence for association with a disorder. The family was not reported to have other affected members. As the authors noted, the boy was not known to have the multi-endocrine abnormalities reported by Tata et al. There are no additional information provided (eg. on confirmation of variants, etc). ----------- [3] Esposito et al. (2019 - PMID: 31688942) report on 3 sibling pairs (all 3 families unrelated) with biallelic DMXL2 mutations and summarize previous evidence on the gene and the DMXL2-related phenotypes. All presented a highly similar phenotype of Ohtahara syndrome (seizures with onset in the first days of life, tonic/myoclonic/occasionaly focal, burst-suppression upon EEG), profound DD/ID, quadriparesis, sensorineural hearing loss and presence of dysmorphic features. Sibs from 2 families presented evidence of peripheral polyneuropathy. Early brain MRIs revealed thin CC and hypomyelination in all, with later scans suggestive of gray and white matter shrinkage with leukoencephalopathy. None achieved developmental skills following birth with 5/6 deceased by the age of 9 years. Exome sequencing revealed biallelic DMXL2 variants in all, with compatible parental segregation studies (NM_015263.3): - Fam1 (2 sibs) : c.5135C>T (p.Ala1712Val) in trans with c.4478C>G (p.Ser1493) - Fam2 (2 sibs) : homozygosity for c.4478C>A (p.Ser1493) - Fam3 (2 sibs) : homozygosity for c.7518-1G>A Heterozygous parents (aged 39-59) did not exhibit hearing impairment [report of a single multigenerational family by Chen et al (2017 - PMID: 27657680) where a heterozygous missense variant segregated with hearing loss - respective OMIM entry: ?Deafness, autosomal dominant 71 - 617605]. In patients' fibroblasts, effect of the variants on mRNA/protein expression was demonstrated with mRNA expressed only in a patient from family 1, and degraded/absent for the 2 stopgain SNVs affecting codon 1493. Skipping of ex31 leading to frameshift/introduction of a PTC was shown for the splice variant (p.Trp2508Argfs4 secondary to c.7518-1G>A). Protein was also absent upon western-blot. DMXL2 encodes a vesicular protein, DmX-Like protein 2 or rabconnectin-3a (cited Tata et al). The gene is expressed in brain ( https://www.gtexportal.org/home/gene/DMXL2 ). As Esposito et al comment, it is known to regulate the trafficking and activity of v-ATPase the latter having a role in acidifying intracellular organelles and promoting endosomal maturation (cited PMIDs : 25248098, 19758563, 22875945, 24802872). In line with this, staining of patients' fibroblasts using the acidotropic dye LysoTracker demonstrated increased signal, reversed by re-expression of DMXL2 protein. Overall an acidic shift in pH with impairment of lysosomal structures and function was suggested. The authors provided additional evidence for altered lysosomal function and associated autophagy with accumulation of autophagy receptors (eg p62) and substrates (polyubiquitinated proteins). Vacuolization and accumulation of atypical fusion-like structures was shown upon ultrastractural analysis. shRNA-mediated downregulation/silencing of Dmxl2 in mouse hippocampal neurons resulted also in altered lysosomal structures and defective autophagy. The neurons exhibited impaired neurite elongation and synapse formation. The authors suggest similarities with Vici syndrome, where biallelic EPG5 mutations result in autophagic defects and clinical manifestations of DD/ID/epilepsy. Dmxl2 homozygous ko mice display embryonic lethality with heterozygous mice displaying macrocephaly and corpus callosum dysplasia (cited PMIDs: 25248098, 30735494) . Sources: Literature
21 Nov 2019	Early onset or syndromic epilepsy v1.425	ALG8	Rebecca Foulger commented on gene: ALG8: PMID:19688606 (Vesela et al., 2009) present a girl with neonatal onset of CDG. Seizures were present from the first day and the girl died age 2 months from progressive oedema, bleeding and cardio-respiratory insufficiency. She had compound het variants in ALG8 (p.T47P and p.R364X).
21 Nov 2019	Early onset or syndromic epilepsy v1.425	ALG8	Rebecca Foulger commented on gene: ALG8: PMID:23430830 (Millon et al., 2011) report 2 siblings with a congenital glycosylation disorder. Their clinical presentation included seizures. The authors could not identify the genetic deficiency in these patients yet.
21 Nov 2019	Early onset or syndromic epilepsy v1.425	ALG8	Rebecca Foulger commented on gene: ALG8: 26066342 (Hock et al., 2015) describe 3 new patients with ALG8-CDG, provide an update on 2 previous patients and summarise 10 previous patients. The 15 patients total included 4 pairs of siblings. Brain involvement (psychomotor disability or seizures or ataxia or structural anomalies) were seen in 12/13 patients.
21 Nov 2019	Early onset or syndromic epilepsy v1.425	FLNA	Alison Callaway reviewed gene: FLNA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
21 Nov 2019	Early onset or syndromic epilepsy v1.425	CACNA2D2	Zerin Hyder reviewed gene: CACNA2D2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30410802, PMID: 31402629, PMID: 24358150, PMID: 23339110, PMID: 29997391; Phenotypes: epilepsy, ataxia, developmental delay, cerebellar atrophy; Mode of inheritance: None
21 Nov 2019	Early onset or syndromic epilepsy v1.425	SLC6A19	Rebecca Foulger Phenotypes for gene: SLC6A19 were changed from to Hartnup disorder, 234500
21 Nov 2019	Early onset or syndromic epilepsy v1.424	SLC6A19	Rebecca Foulger Publications for gene: SLC6A19 were set to
21 Nov 2019	Early onset or syndromic epilepsy v1.423	SLC6A19	Rebecca Foulger commented on gene: SLC6A19: PMID:20399395 (Cheon et al 2010) report a Korean boy age 8 years and 5 months with Hartnup disorder. He had seizures, ADHD and mental retardation. Genetic analysis revealed novel compound het variants in SLC6A19: p.Thr596fsX73 and p.Ser303Leu.
21 Nov 2019	Early onset or syndromic epilepsy v1.423	SCO2	Rebecca Foulger commented on gene: SCO2: PMID:18924171 (Verdijk et al, 2008) report compound het SOC2 variants (E140K and W36X) in 2 siblings with fatal infantile cardioencephalomyopathy. The index patient had convulsions age 1 day and died of heart failure age 25 days. The sibling fetus was terminated at 23 weeks following genetic testing.
21 Nov 2019	Early onset or syndromic epilepsy v1.423	SCO2	Rebecca Foulger commented on gene: SCO2: PMID:10749987 (Jaksch et al., 2000) report 10 patients with fatal hypertrophic cardiomyopathy from 9 families. Mutations in SCO2 (E140K, R171W) were found in 3 patients (2 unrelated families) all of whom had seizures: Table 1.
21 Nov 2019	Early onset or syndromic epilepsy v1.423	SCO2	Rebecca Foulger commented on gene: SCO2: PMID:10545952 (Papadopoulou et al 1999) identified variants in SCO2 in 3 unrelated infants with fatal cardioencephalomyopathy and COX deficiency. Patient 2 had focal epileptiform discharges on an EEG.
21 Nov 2019	Early onset or syndromic epilepsy v1.423	SCO1	Rebecca Foulger commented on gene: SCO1: PMID:22231385 (Honzik et al., 2012) summarise 461 patients with mitochondrial disorders. One patient had a variant in SCO1: seizures were not a feature (Table 2, Stiburek et al., 2009).
21 Nov 2019	Early onset or syndromic epilepsy v1.423	SCO1	Rebecca Foulger changed review comment from: PMID:15023375 report an 8-week old infant who presented with neonatal seizures and limb malformations. There were multiple seizure types, including multifocal myoclonus, complex partial events and generalised tonic–clonic episodes. Treatment of seizures was of limited success. The specific defect seen in the patient was a complex IV deficiency. Although no known variants were identified, the clinical picture overlaps with the SCO1 presentation.; to: PMID:15023375 (Kurian et al., 2004) report an 8-week old infant who presented with neonatal seizures and limb malformations. There were multiple seizure types, including multifocal myoclonus, complex partial events and generalised tonic–clonic episodes. Treatment of seizures was of limited success. The specific defect seen in the patient was a complex IV deficiency. Although no known variants were identified, the clinical picture overlaps with the SCO1 presentation.
21 Nov 2019	Early onset or syndromic epilepsy v1.423	SCO1	Rebecca Foulger Publications for gene: SCO1 were set to 23878101; 11013136; 19295170
21 Nov 2019	Early onset or syndromic epilepsy v1.422	SCO1	Rebecca Foulger changed review comment from: PMID:23878101 (Leary et al., 2013) report compound het variants in SCO1 in a patient with fatal encephalopathy. The patient developed seizures age 4 months which were difficult to control. He died age 5 months (Supporting information).; to: PMID:23878101 (Leary et al., 2013) report compound het variants in SCO1 in a patient with fatal encephalopathy. The patient developed seizures age 4 months which were difficult to control. He died age 5 months (seizure information and extended clinical phenotype is the supporting information).
21 Nov 2019	Early onset or syndromic epilepsy v1.422	SCO1	Rebecca Foulger commented on gene: SCO1: PMID:15023375 report an 8-week old infant who presented with neonatal seizures and limb malformations. There were multiple seizure types, including multifocal myoclonus, complex partial events and generalised tonic–clonic episodes. Treatment of seizures was of limited success. The specific defect seen in the patient was a complex IV deficiency. Although no known variants were identified, the clinical picture overlaps with the SCO1 presentation.
21 Nov 2019	Early onset or syndromic epilepsy v1.422	SCO1	Rebecca Foulger commented on gene: SCO1: PMID:23878101 (Leary et al., 2013) report compound het variants in SCO1 in a patient with fatal encephalopathy. The patient developed seizures age 4 months which were difficult to control. He died age 5 months (Supporting information).
21 Nov 2019	Early onset or syndromic epilepsy v1.422	QDPR	Rebecca Foulger Phenotypes for gene: QDPR were changed from Hyperphenylalaninemia, BH4-deficient, C, 261630 to Hyperphenylalaninemia, BH4-deficient, C, 261630; DHPR deficiency
21 Nov 2019	Early onset or syndromic epilepsy v1.421	QDPR	Rebecca Foulger Publications for gene: QDPR were set to 9341885; 26006720
21 Nov 2019	Early onset or syndromic epilepsy v1.420	QDPR	Rebecca Foulger commented on gene: QDPR: Seizures listed in the OMIM Clinical synopsis for 'Hyperphenylalaninemia, BH4-deficient, C' (MIM:261630).
21 Nov 2019	Early onset or syndromic epilepsy v1.420	QDPR	Rebecca Foulger commented on gene: QDPR: Ikeda et al. (1997, PMID:9341885) report a Japanese boy with hyperphenylalaninemia and a splicing error variant in QDPR. He was the offspring of first-cousin parents. The patient showed intractable seizures and developmental delay.
21 Nov 2019	Early onset or syndromic epilepsy v1.420	PRODH	Rebecca Foulger Publications for gene: PRODH were set to 12217952
21 Nov 2019	Early onset or syndromic epilepsy v1.419	PRODH	Rebecca Foulger commented on gene: PRODH: PMID:17412540 (Afenjar et al 2007) report 4 unrelated children and biallelic variants in PRODH. The authors note that 4 previous patients had been reported (Jacquet et al, 2002, 2003 and Raux et al 2007) and of the 8 total patients, 5 had epilepsy (plus febrile case), often severe with status epilepticus.
21 Nov 2019	Early onset or syndromic epilepsy v1.419	PRODH	Rebecca Foulger commented on gene: PRODH: PMID:18197084 (Di Rosa et al., 2008) screened 4 unrelated Italian children all of whom presented with epilepsy and ID, and compound het/homozygous variants in PRODH. Functional tests to confirm the pathogenicity were not performed.
21 Nov 2019	Early onset or syndromic epilepsy v1.419	PRODH	Rebecca Foulger Publications for gene: PRODH were set to
21 Nov 2019	Early onset or syndromic epilepsy v1.418	PEX1	Rebecca Foulger commented on gene: PEX1: PMID:16141001 (Rosewich et al 2005) studied 33 patients with PEX1 variants. Seizures are a feature in Table 3 for 6 patients.
21 Nov 2019	Early onset or syndromic epilepsy v1.418	PEX1	Rebecca Foulger Publications for gene: PEX1 were set to 12402331; 26387595; 9398847
21 Nov 2019	Early onset or syndromic epilepsy v1.417	PEX1	Rebecca Foulger commented on gene: PEX1: PMID:15098231 (Poll-The BT et al 2004) surveyed 31 patients with a generalized peroxisomal disorder from 27 families. 7/31 patients (23%) developed seizures from 0 - 2.7 years. Most patients (60-70%) had variants in the PEX1 gene. Most frequent variants include G843D and frameshift c.2097insT.
21 Nov 2019	Early onset or syndromic epilepsy v1.417	PEX1	Rebecca Foulger commented on gene: PEX1: PMID:15301838 (Michelakakis et al, 2004) decribe a female patient of healthy unrelated patients. Her diagnosis of Leber congenital amaurosis was subsequently demonstrated to be a PEX1 defect. Myoclonic seizures began age 2. The patient is heterozygous for G843D variant and an additional second variant that is not yet identified.
21 Nov 2019	Early onset or syndromic epilepsy v1.417	PEX1	Rebecca Foulger commented on gene: PEX1: PMID:28432012 (Ge et al., 2017) report 2 Chinese newborns with Zellweger phenotypes and compound het variants in PEX1 (Arg577Thrfs15 and Asn830Thrfx61). Although the authors note that seizures are in the clinical spectrum of ZS patients, seizures were not reported for the Chinese newborns.
21 Nov 2019	Early onset or syndromic epilepsy v1.417	PEX1	Rebecca Foulger commented on gene: PEX1: PMID:21844578 (Cho et al., 2011) report a Korean patient who was compound het for variants in the PEX1 gene (p.H678QfsX3 and p.R949W) inherited from the parents. He had typical features of ZS including seizures (starting 4 days old), dysmorphic face and a poor suck.
21 Nov 2019	Early onset or syndromic epilepsy v1.417	MTR	Rebecca Foulger commented on gene: MTR: PMID:28666289 (Komulainen-Ebrahim et al., 2017) describe a homozygous MTR p.P1173L variant in a patient with drug-resistant seizures associated with hyperhomocysteinemia and hypomethioninemia.
21 Nov 2019	Early onset or syndromic epilepsy v1.417	MTR	Rebecca Foulger commented on gene: MTR: PMID:9683607 (Wilson et al., 1998) report 3 cblG patients, including 2 siblings who presented with neonatal seizures.
21 Nov 2019	Early onset or syndromic epilepsy v1.417	MTR	Rebecca Foulger commented on gene: MTR: PMID:25526710 (Huemer et al., 2015) summarise clinical features of 13 patients with the cblG defect (caused by defects in MTR): 5/13 had seizures.
21 Nov 2019	Early onset or syndromic epilepsy v1.417	IDH2	Rebecca Foulger commented on gene: IDH2: A number of papers note that IDH1 and IDH2 variants have an established association with preoperative seizures in patients with grade II-IV diffuse gliomas (PMID:29172136, 29288860, 22217666).
21 Nov 2019	Early onset or syndromic epilepsy v1.417	IDH2	Rebecca Foulger Publications for gene: IDH2 were set to 20847235
21 Nov 2019	Early onset or syndromic epilepsy v1.416	IDH2	Rebecca Foulger commented on gene: IDH2: PMID:24049096 (Nota et al., 2013) report 3 cases, with seizures reported in 2/3. Case 2 was a 9 year old Caucasian girl with tonic-clonic seizures and mosaic IDH2 variants. Case 3 was a Caucasian girl with seizures age 3 months- her seizures responded well to anticonvulsants. The patient died from sudden cardiac arrest age 8, and was found to have a heterozygous IDH2 c.419G>A variant. Germline mosaicism in the mother was suggested to explain the inheritance pattern in this family.
21 Nov 2019	Early onset or syndromic epilepsy v1.416	HLCS	Rebecca Foulger commented on gene: HLCS: PMID:27114915 (Donti et al., 2016) describe a cohort of 5 patients. Case 5 had focal seizures age 5 months which have continued since. He has compound het variants in HLCS (N570K and c.1519+5G>A). The authors note that the phenotypic spectrum of HCLS is broad, from intractable seizures and ID to normal growth and development.
21 Nov 2019	Early onset or syndromic epilepsy v1.416	GSS	Rebecca Foulger Publications for gene: GSS were set to 26984560
21 Nov 2019	Early onset or syndromic epilepsy v1.415	GSS	Rebecca Foulger commented on gene: GSS: PMID:26669244 (Gunduz et al., 2016) report 4 patients with GS deficiency. Case I and Case IV had seizures noted together with homozygous variants (splicing variant in I and p.R125H in IV): Table 1.
21 Nov 2019	Early onset or syndromic epilepsy v1.415	GSS	Rebecca Foulger commented on gene: GSS: Seizures are recorded in OMIM Clinical synopsis for MIM:266130 based on Marstein et al., 1976 (no PubMed).
21 Nov 2019	Early onset or syndromic epilepsy v1.415	GSS	Rebecca Foulger commented on gene: GSS: PMID:15990954 (Njallson et al 2005) summarise the phenotypes of patients with glutathione synthetase deficiency, but don't mention seizures or epilepsy (as noted in review by Tracy Lester).
21 Nov 2019	Early onset or syndromic epilepsy v1.415	GSS	Rebecca Foulger commented on gene: GSS: PMID:11445798 (Ristoff et al,. 2001) examined 28 patients with Glutathione synthetase deficiency (GSSD). Diagnosis was based on metabolic tests. 16/28 had neurological symptoms such as seizures/psychomotor retardation. In 16 patients with severe GS deficiency, 7 had seizures.
21 Nov 2019	Early onset or syndromic epilepsy v1.415	GSS	Rebecca Foulger commented on gene: GSS: PMID:26984560 (Atwal et al. 2016) present a 19 year old female with Glutathione synthetase deficiency (GSSD). She was diagnosed with a mild seizure disorder age 10, and treated with the antiepileptic lamotrigine, which was discontinued once she was seizure free for 5 years. The authors note it is possible her seizures were unrelated to the underlying GSSD.
21 Nov 2019	Early onset or syndromic epilepsy v1.415	GSS	Rebecca Foulger Publications for gene: GSS were set to
21 Nov 2019	Early onset or syndromic epilepsy v1.414	GLYCTK	Rebecca Foulger Publications for gene: GLYCTK were set to 3588091; 30637540; 28462797; 20949620
21 Nov 2019	Early onset or syndromic epilepsy v1.413	GLYCTK	Rebecca Foulger Publications for gene: GLYCTK were set to 3588091
21 Nov 2019	Early onset or syndromic epilepsy v1.412	GLYCTK	Rebecca Foulger commented on gene: GLYCTK: PMID:30637540 (Zehavi et al., 2019) report a male from a consanguineous Arab family with intractable seizures and a homozygous missense pathogenic variant in GLYCTK (p.Leu152Pro).
21 Nov 2019	Early onset or syndromic epilepsy v1.412	GLYCTK	Rebecca Foulger commented on gene: GLYCTK: PMID:28462797 (Swanson et al., 2017) reviewed the Serbian patient from Sass et al., 2010. In addition to p.Phe483SerfsX2 variant in GLYCTK, the patient had an additional Ser117Leu variant in AMT highlighting the co-occurence of two metabolic conditions (D-glyceric aciduria and nonketotic hyperglycinemia).
21 Nov 2019	Early onset or syndromic epilepsy v1.412	GLYCTK	Rebecca Foulger commented on gene: GLYCTK: PMID:20949620 (Sass et al., 2010) report 3 patients of Serbian, Mexican and Turkish origin, including the original 1974 (Serbian) patient. All had homozygous variant in GLYTCK: Patient A was a Serbian boy with generalized seizures beginning age 8 weeks (p.Phe483SerfsX2 variant). Patient B was a Mexican girl with focal clonic seizures and a Phe493Cys variant. Patient C was a Turkish boy where seizures were not noted (p.Leu520CysfsX108 variant).
21 Nov 2019	Early onset or syndromic epilepsy v1.412	GFM1	Rebecca Foulger Publications for gene: GFM1 were set to 25852744; 26937387; 28216230; 23430926; 21986555
21 Nov 2019	Early onset or syndromic epilepsy v1.411	GFM1	Rebecca Foulger commented on gene: GFM1: PMID:28216230 (Simon et al., 2017) report 2 brothers with compound het variants in GFM1 (maternally-inherited p.Arg250Trp and paternally-inherited p.Gly230_231Glnins19). The younger brother (P1) developed seizures by 4.5 months, characterised as infantile spasms. He has remained seizure free on treatment with topiramate. No seizures were noted for the brother who died age 10 months from multiple organ failure. The authors suggest additional modifier genes may be responsible for the different in severity between the brothers.
21 Nov 2019	Early onset or syndromic epilepsy v1.411	GFM1	Rebecca Foulger commented on gene: GFM1: PMID:26937387 (Ravn et al., 2015) describe 3 patients with novel GFM1 variants. Patient 3 (a girl of non-consanguineous parents) had epileptic seizures beginning at 2 months old. She died at 3 months during a febrile episode.
21 Nov 2019	Early onset or syndromic epilepsy v1.411	GFM1	Rebecca Foulger commented on gene: GFM1: PMID:21986555. Galmiche et al., 2012 report two unrelated patients with homozygous GFM1 variants (R671C). The parents were both heterozygous for this variant For the first patient (an Algerian boy from consanguineous parents), no clinical seizures were noted but EEG showed burst of multifocal spikes.
21 Nov 2019	Early onset or syndromic epilepsy v1.411	GFM1	Rebecca Foulger commented on gene: GFM1: PMID:25852744. Brito et al., 2015 report an infant born to unrelated Caucasian parents with seizures amongst her phenotype (starting age 7 months) and compound het variants in GFM1 (Gly469Valfs*84 and Arg671Cys). The authors summarise clinical features of previous GFM1-deficient patients and note seizures in 5/12 patients.
21 Nov 2019	Early onset or syndromic epilepsy v1.411	GFM1	Rebecca Foulger commented on gene: GFM1: PMID:21119709. In a girl, born of consanguineous parents, with combined oxidative phosphorylation deficiency, Smits et al. (2011) identified a homozygous R250W variant in GFM1. The patient had refractory seizures amongst her phenotypes. This paper is referred to in the review by Tracy Lester.
21 Nov 2019	Early onset or syndromic epilepsy v1.411	GCH1	Rebecca Foulger Publications for gene: GCH1 were set to 7869202; 17407085; 12552057; 7730309; 31202265
21 Nov 2019	Early onset or syndromic epilepsy v1.410	GCH1	Rebecca Foulger Publications for gene: GCH1 were set to 7869202; 17407085; 12552057; 7730309
21 Nov 2019	Early onset or syndromic epilepsy v1.409	GCH1	Rebecca Foulger commented on gene: GCH1: Additional evidence for seizures being part of the metabolic disorder comes from PMID:31202265 (Dayasiri et al, 2019) who report a S. Asian child with AR GTPCH (GCH1) deficiency, diagnosed from metabolic testing and family consanguinity. Features included recurrent seizures since 3 months old.
21 Nov 2019	Early onset or syndromic epilepsy v1.409	GCH1	Rebecca Foulger Publications for gene: GCH1 were set to 7869202; 17407085; 12552057
19 Nov 2019	Early onset or syndromic epilepsy v1.408	HCN2	Rebecca Foulger Added comment: Comment on mode of inheritance: Kept MOI as 'BOTH monoallelic and biallelic' as supported by reviews from Helen Lord and Alison Callaway, and literature (PMID:22131395).
19 Nov 2019	Early onset or syndromic epilepsy v1.408	HCN2	Rebecca Foulger Mode of inheritance for gene: HCN2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
13 Nov 2019	Early onset or syndromic epilepsy v1.407		Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease; GMS Rare Disease Virtual
13 Nov 2019	Early onset or syndromic epilepsy v1.406		Ellen McDonagh List of related panels changed from Epilepsy Plus; Epilepsy plus other features; Genetic Epilepsy Syndromes; Epileptic encephalopathy; Familial Focal Epilepsies; Familial Genetic Generalised Epilepsies; Genetic Epilepsies with Febrile Seizures Plus (GEFS+); Genetic Epilepsies with Febrile Seizures Plus; Early onset or syndromic epilepsy to Epilepsy Plus; Epilepsy plus other features; Genetic Epilepsy Syndromes; Epileptic encephalopathy; Familial Focal Epilepsies; Familial Genetic Generalised Epilepsies; Genetic Epilepsies with Febrile Seizures Plus (GEFS+); Genetic Epilepsies with Febrile Seizures Plus; Early onset or syndromic epilepsy; R59
11 Nov 2019	Early onset or syndromic epilepsy v1.405	NSF	Konstantinos Varvagiannis gene: NSF was added gene: NSF was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: NSF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: NSF were set to 31675180 Phenotypes for gene: NSF were set to Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability Penetrance for gene: NSF were set to unknown Review for gene: NSF was set to AMBER Added comment: Suzuki et al. (2019 - PMID: 31675180) report on 2 unrelated individuals with de novo missense NSF variants. Overall the phenotype corresponded to an early infantile epileptic encephalopathy. The first patient developed vomiting and tonic seizures immediately after birth, with burst-suppression pattern upon EEG. Trio exome sequencing, followed by Sanger sequencing of proband and parents, revealed a de novo missense variant (NM_006178.3:c.1375G>A / p.Ala459Thr), absent from public databases and predicted in silico to be deleterious (CADD score of 30). The girl died 36 days after birth due to respiratory failure. Another subject, having necessitated mechanical ventilation due to absence of spontaneous respiration after birth, developed myoclonic seizures. EEG showed a burst-suppression pattern. At the age of 3, she was noted to have persistence of seizures and profound ID. Trio exome sequencing identified a missense NSF variant (c.1688C>T / p.Pro563Leu) also confirmed and shown to be de novo by Sanger sequencing. Again the variant was absent from public datasets and had a CADD score of 34. While expression of wt NSF allele in the developing eye of Drosophila had no effect, expression of mutants severely affected eye development - suggesting a dominant negative effect. NSF encodes a homo-hexameric AAA ATPase, which is recruited by SNAPs (Soluble NSF Attachment Proteins) - and the latter by SNAREs (SNAP REceptors) - thus having a role in vesicular transport and membrane fusion. There is currently no associated phenotype in OMIM/G2P. Overall, this gene could be considered for inclusion probably with amber/red rating pending further evidence (eg. additional work-up or alternative causes/explanations not discussed). Sources: Literature
11 Nov 2019	Early onset or syndromic epilepsy v1.405	SCAMP5	Konstantinos Varvagiannis gene: SCAMP5 was added gene: SCAMP5 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: SCAMP5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SCAMP5 were set to 31439720; 20071347 Phenotypes for gene: SCAMP5 were set to Global developmental delay; Intellectual disability; Seizures; Abnormality of nervous system morphology; Behavioral abnormality Penetrance for gene: SCAMP5 were set to unknown Mode of pathogenicity for gene: SCAMP5 was set to Other Review for gene: SCAMP5 was set to AMBER Added comment: PMID: 31439720 (Hubert et al. 2019) reported on 2 unrelated individuals with severe ID, seizures, behavioral and brain MRI abnormalities (white matter hyperintensity and mesial temporal sclorosis), both harboring the same missense SCAMP5 mutation as a de novo event (NM_001178111.1:c.538G>T or p.Gly180Trp). Previously aCGH +/- metabolic workup were non diagnostic. The occurrence of the same de novo variant in both as well as the similar presentation (incl. MRI images) suggested SCAMP5 as the most probable candidate gene, despite presence of few other variants in both. SCAMP5 is highly expressed in brain (https://www.proteinatlas.org/ENSG00000198794-SCAMP5) and previous studies have suggested a role in synaptic vesicle trafficking (PMIDs cited: 29562188, 25057210, etc). Cultured skin fibroblasts from affected individuals failed to express SCAMP5. Scamp is the Drosophila orthologue, with previous studies having demonstrated that mutants display defects in climbing, olfactory-assisted memory and susceptibility to heat induced seizures (PMIDs cited: 25478561, 19144841). Expression of the Scamp Gly302Trp variant in Drosophila ('equivalent' to the SCAMP5 Gly180Trp) revealed strongly reduced levels for the variant compared with wt upon Western Blot, either due to reduced expression or due to increased turnover. Overall the effect of Gly302Trp expression was similar to Scamp knockdown by RNAi (eg. rough eye phenotype, reduced ability to climb the walls of a graded tube after tapping, less/no flies reaching adult stage) but significantly different compared to wt. As a result, a dominant-negative effect was presumed. ---------- PMID: 20071347 (Castermans et al. 2010) is cited as a previous report of a relevant affected individual. In this study a 40 y.o. male with early DD, mild ID (IQ of 63) and ASD was found to harbor a de novo apparently balanced t(1;15) translocation affecting CLIC4 and PPCDC (both not associated with ID). [1-Mb resolution aCGH revealed no relevant CNVs]. Studies were however focused on SCAMP5 given that the gene is located downstream of / proximal to PPCDC, has brain-enriched expression as well as involvement in synaptic trafficking and demonstrated: - Less than 50% expression upon quantitative RT-PCR in patients leukocytes, compared to control. - Silencing and overexpression of Scamp5 in mouse β-TC3 cells resulted in increased and suppressed respectively secretion of large dense-core vesicles (LDCVs). - Given conservation of some components involved in secretion of dense core granules (DCGs) in platelets and LDCVs in neuronal cells, study of patient platelets - where SCAMP5 was confirmed to be expressed - suggested an altered pattern of DCGs. ---------- SCAMP5 is not associated with any phenotype in OMIM/G2P/SysID and not commonly included in gene panels for ID. ---------- Overall, this gene could be considered for inclusion in the ID and epilepsy panels probably with amber (# of unrelated individuals, 1 recurrent de novo variant and 1 regulatory effect, gene expressed in brain with a role in synaptic vesicle trafficking) or red rating (pending further evidence). Sources: Literature
11 Nov 2019	Early onset or syndromic epilepsy v1.405	PCYT2	Konstantinos Varvagiannis gene: PCYT2 was added gene: PCYT2 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: PCYT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PCYT2 were set to 31637422 Phenotypes for gene: PCYT2 were set to Global developmental delay; Developmental regression; Intellectual disability; Spastic paraparesis; Seizures; Cerebral atrophy; Cerebellar atrophy Penetrance for gene: PCYT2 were set to Complete Review for gene: PCYT2 was set to GREEN Added comment: Vaz et al. (2019 - PMID: 31637422 - DDD study among the co-authors) report on 5 individuals - from 4 families - with biallelic PCYT2 mutations. The phenotype corresponded to a complex hererditary paraplegia with global DD, regression (4/5), ID (mild in 3/5, severe in 2/5), spastic para-/tetraparesis, epilepsy (5/5 - variable onset 2-16 yrs - focal or tonic-clonic seizures) and progressive cerebral and cerebellar atrophy. Exome sequencing in all revealed biallelic PCYT2 variants, confirmed with Sanger s. in probands and their parents (NM_001184917.2 - corresponding to the canonical transcript used as Ref below): - P1 (Fam1) : 2 missense SNVs in trans configuration, c.730C>T or p.His244Tyr and c.920C>T or p.Pro307Leu - P2 (Fam2 - consanguineous of White British origin), P3 (Fam3 - Consanguineous of Turkish origin), P4,5 (Fam4 - consanguineous, unspecified origin) : homozygosity for c.1129C>T or p.Arg377Ter) affecting the last exon of 8/12 transcripts, including the canonical one. Individuals with the same genotype displayed variable degrees of ID (eg P3 - severe / P2, P4,5 - mild ID). For sibs in Fam4, homozygosity for a missense SACS variant led to consideration of the respective disorder (AR spastic ataxia of Charlevoix-Saguenay) though the variant was predicted to be tolerated in silico and notably the MRI images not suggestive. All variants were absent from / had extremely low AF in public databases, with no homozygotes. Posphatidylethanolamine (PE) is a membrane lipid, particularly enriched in human brain (45% of phospholypid fraction). PE is synthesized either via the CDP-ethanolamine pathway or by decarboxylation of phosphatidylserine in mitochondria. PCYT2 encodes CTP:phosophoethanolamine cytidyltransferase (ET) which is an ubiquitously expressed rate-limiting enzyme for PE biosynthesis in the former pathway. In silico, the 2 missense variants - localizing in the CTP catalytic domain 2 - were predicted to be damaging, as well as to affect protein stability. Fibroblasts of 3 patients (P1, P2, P3) representing all variants were studied: - Enzymatic activity was shown to be significantly reduced (though not absent) compared to controls. Abnormalities were noted upon Western Blot incl. absence in all 3 patients studied of one of the 2 bands normally found in controls (probably representing the longer isoform), reduced intensity in all 3 of another band probably corresponding to a shorter isoform, and presence of an additional band of intermediate molec. mass in patients with the truncating variant. - RT-PCR on mRNA from patient fibroblasts did not reveal (significant) reduction compared to controls. - Lipidomic profile of patient fibroblasts was compatible with the location of the block in the phospholipid biosynthesis pathway and different from controls. The lipidomic profile had similarities with what has been reported for EPT1 deficiency, the enzyme directly downstream of ET. The SELENO1-related phenotype (/EPT1 deficiency) is also highly overlapping. CRISPR-Cas9 was used to generate pcyt2 partial or complete knockout (ko) zebrafish, targeting either the final (ex13) or another exon (ex3) respectively. mRNA expression was shown to be moderately reduced in the first case and severely reduced/absent in the second, compared to wt. Similarly, complete-ko (ex3) led to significantly lower survival, with impaired though somewhat better survival of partial-ko (ex13) zebrafish. Complete knockout of Pcyt2 in mice is embryonically lethal (PMID cited: 17325045) while heterozygous mice develop features of metabolic syndrome (PMID cited: 22764088). Given lethality in knockout zebrafish / mice and the residual activity (15-20%) in patient fibroblasts, the variants reported were thought to be hypomorphic and complete loss of function possibly incompatible with life. PCYT2 is not associated with any phenotype in OMIM/G2P/SysID and not commonly included in gene panels for ID. As a result this gene could included in the ID / epilepsy panels with green (~/>3 indiv/fam/variants with the nonsense found in different populations, consistent phenotype, lipidomics, in silico/in vitro/in vivo evidence) or amber rating. [Please consider inclusion in other possibly relevant panels eg. for metabolic disorders, etc]. Sources: Literature
11 Nov 2019	Early onset or syndromic epilepsy v1.405	FDFT1	Konstantinos Varvagiannis gene: FDFT1 was added gene: FDFT1 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: FDFT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FDFT1 were set to 29909962 Phenotypes for gene: FDFT1 were set to Profound global developmental delay; Intellectual disability; Seizures; Abnormality of nervous system morphology; Cortical visual impairment; Abnormality of the skin; Abnormality of the face Penetrance for gene: FDFT1 were set to Complete Review for gene: FDFT1 was set to AMBER Added comment: Biallelic pathogenic FDFT1 variants cause Squalene synthase deficiency (MIM 618156). 3 individuals from 2 families (and 3 variants) have been reported. DD, ID and seizures are part of the phenotype (3/3). The metabolic profile observed is specific and highly suggestive of disruption of the cholesterol biosynthesis pathway (at the specific level) while the clinical presentation is similar to other disorders of the pathway (SLO). The effect of 2 variants has been studied in detail (in one case mis-splicing demonstrated and in the other regulatory effect). Overall, this gene could be considered for inclusion in the ID/epilepsy panel with amber rating. As the gene is currently present only in the DDG2P panel, please consider adding it to relevant ones (eg. IEMs, undiagnosed metabolic disorders, etc). [Details provided below]. ---- Coman et al. (2018 - PMID: 29909962) reported on 3 relevant individuals from 2 unrelated families. The phenotype consisted of seizures (3/3 - neonatal onset - generalized), profound DD (ID can be inferred from the description in the supplement), variable brain MRI abnormalities (white matter loss, hypoplastic CC), cortical visual impairment, dry skin with photosensitivity as well facial dysmorphic features. Male subjects presented genital anomalies (cryptorchidism/hypospadias). FDFT1 encodes squalene synthase, the enzyme which catalyzes conversion of farnesyl-pyrophosphate to squalene - the first specific step in cholesterol biosynthesis. A specific pattern of metabolites was observed in all, similar to a pattern previously observed in animal models/humans treated with squalene synthase inhibitor or upon loading with farnesol (in animals). Overall the pattern was suggestive of a cholesterol biosynthesis defect at the level of squalene synthase as suggested by increased total farnesol levels (farnesyl-pyrophosphate + free farnesol), reduced/normal squalene, low plasma cholesterol as well as other metabolites. Clinical features also resembled those observed in Smith-Lemli-Opitz syndrome (another disorder of cholesterol biosynthesis). WES was carried out in affected individuals and their parents and revealed for sibs of the first family, compound heterozygosity for a maternally inherited 120-kb deletion spanning exons 6-10 of FDFT1 and CTSB and a paternally inherited FDFT1 variant in intron 8 (TC deletion/AG insertion). Variant studies for the latter included: - Minigene splice assay demonstrating retention of 22 bp in intron 8. - Partial splicing defect with both nl and mis-spliced cDNA (patient fibroblasts) - Reduced protein levels in lymphoblasts/fibroblasts from both sibs upon Western blot. Contribution of the CTSB deletion was considered unlikely (carrier mother was unaffected). As for the 2nd family, WES data allowed identification of a homozygous deep-intronic (although this is transcript-specific) 16-bp deletion in the proband. Parents were carriers. For the specific variant : - cDNA studies failed to detect 3 (of 10) isoforms which are normally present in control fibroblasts. Eventual NMD (which would be predicted if the deletion resulted in splicing defect) was eliminated given the absent effect of cyclohexamide addition, thus suggesting a regulatory effect. - Given a predicted promoter/enhancer effect of the deleted region, a luciferase assay performed, suggested that the sequence had promoter capacity, with the construct containing the 16-bp deletion showing reduced promoter activity. Fdft1 knockout mice demonstrate embryonic lethality around mid-gestation while they exhibit severe growth retardation and defective neural tube closure. In G2P FDFT1 is associated with 'Defect in Cholesterol Biosynthesis' (confidence:possible/biallelic/LoF). The gene belongs to the Current primary ID gene group of SysID. It is not commonly included in gene panels for ID offered by diagnostic laboratories. Sources: Literature
07 Nov 2019	Early onset or syndromic epilepsy v1.405	GOT2	Rebecca Foulger commented on gene: GOT2
07 Nov 2019	Early onset or syndromic epilepsy v1.405	HNRNPR	Rebecca Foulger commented on gene: HNRNPR
07 Nov 2019	Early onset or syndromic epilepsy v1.405	HLCS	Rebecca Foulger Publications for gene: HLCS were set to
07 Nov 2019	Early onset or syndromic epilepsy v1.404	HLCS	Rebecca Foulger Phenotypes for gene: HLCS were changed from to Holocarboxylase synthetase deficiency, 253270
07 Nov 2019	Early onset or syndromic epilepsy v1.403	PLA2G6	Rebecca Foulger Classified gene: PLA2G6 as Amber List (moderate evidence)
07 Nov 2019	Early onset or syndromic epilepsy v1.403	PLA2G6	Rebecca Foulger Added comment: Comment on list classification: Although PLA2G6 is Green on the 'Inborn errors of metabolism' panel, have added to the Epilepsy panel as Amber as unclear if seizures are a consistent feature. Requires clinical review (and review of the MOI in PMID:27513994) before promotion to Green.
07 Nov 2019	Early onset or syndromic epilepsy v1.403	PLA2G6	Rebecca Foulger Gene: pla2g6 has been classified as Amber List (Moderate Evidence).
07 Nov 2019	Early onset or syndromic epilepsy v1.402	PLA2G6	Rebecca Foulger Added comment: Comment on mode of inheritance: Selected 'BIALLELIC' inheritance to match the metabolism PanelApp panels (including Inborn errors of metabolism, V1.392), all OMIM disorders and both G2P disorders. However, PMID:27513994 report autosomal dominant inheritance for Familial cortical myoclonic tremor with epilepsy (FCMTE).
07 Nov 2019	Early onset or syndromic epilepsy v1.402	PLA2G6	Rebecca Foulger Mode of inheritance for gene: PLA2G6 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
07 Nov 2019	Early onset or syndromic epilepsy v1.401	PLA2G6	Rebecca Foulger commented on gene: PLA2G6: PMID:27513994 (Gao et al., 2016) report a family (41 members) which included 6 individuals affected with Familial cortical myoclonic tremor with epilepsy (FCMTE). All 6 individuals had tremors while 5 individuals had seizures. Genomic sequencing was performed on 3 affected and 2 unaffected individuals. A novel missense variant c.475C>T (p.A159T) in PLA2G6 with AD inheritance was identified in this family which segregated with the disease. Note that a variant in SNRNP200 gene also segregated with the disease but is within the untranslated region and the functional effect is unclear.
07 Nov 2019	Early onset or syndromic epilepsy v1.401	PLA2G6	Rebecca Foulger commented on gene: PLA2G6: PMID:30772976. Ma et al., 2019 analyse a Chinese Han pedigree with seizures amongst the phenotype. Compound het variants in PLA2G6 were found (p.A80T and p.D331Y) (full English text not available).
07 Nov 2019	Early onset or syndromic epilepsy v1.401	PLA2G6	Rebecca Foulger commented on gene: PLA2G6: PMID:30340910. Darling et al., 2019 investigated 16 patients from 13 families with PLA2G6-associated neurodegeneration (an autosomal recessive disorder). Epilepsy was observed in 8/16 patients (7 families, 2 patients had been previously reported, Table 1). All patients harboured missense, nonsense and frameshift variants in PLA2G6.
07 Nov 2019	Early onset or syndromic epilepsy v1.401	PLA2G6	Rebecca Foulger gene: PLA2G6 was added gene: PLA2G6 was added to Genetic epilepsy syndromes. Sources: Literature,Other Mode of inheritance for gene: PLA2G6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PLA2G6 were set to 30340910; 27513994; 30772976 Phenotypes for gene: PLA2G6 were set to PLA2G6-associated neurodegeneration (PLAN); Familial cortical myoclonic tremor with epilepsy (FCMTE); Infantile neuroaxonal dystrophy 1, 256600; Neurodegeneration with brain iron accumulation 2B, 610217 Added comment: Added to epilepsy panel based on a Green rating on the 'Inborn errors of metabolism panel'- seizures are a reported feature of MIM:256600 and MIM:610217. Sources: Literature, Other
07 Nov 2019	Early onset or syndromic epilepsy v1.400	DNAJC5	Rebecca Foulger Classified gene: DNAJC5 as Green List (high evidence)
07 Nov 2019	Early onset or syndromic epilepsy v1.400	DNAJC5	Rebecca Foulger Added comment: Comment on list classification: Added to panel as a Green gene as seizures are a symptom of the metabolic disorder, and sufficient epilepsy cases from literature.
07 Nov 2019	Early onset or syndromic epilepsy v1.400	DNAJC5	Rebecca Foulger Gene: dnajc5 has been classified as Green List (High Evidence).
07 Nov 2019	Early onset or syndromic epilepsy v1.399	DNAJC5	Rebecca Foulger commented on gene: DNAJC5: PMID:22235333: Velinov et al., 2012. The authors previously described the Parry family in the 1970s. All affected individuals from the family had a history of progressive seizure disorder. They identified a pLeu116del variant in DNAJC5 which segregated with the disease. 8 additional families were studied for this paper, with seizures amongst the phenotypes. In one affected individual, pLeu115Arg was identified (proband BD-319) who had seizures and gradual dementia beginning in the mid 30s.
07 Nov 2019	Early onset or syndromic epilepsy v1.399	DNAJC5	Rebecca Foulger commented on gene: DNAJC5: PMID:29506599: Jarrett et al., 2018 report a family with Kufs disease in which the proband and 3/4 children presented with cognitive impariment, seizures and myoclonus. Genetic testing of all four children was positive for a c.346_348delCTC(p.L116del) variant in the DNAJC5 gene. EEG on the asymptomatic fourth child showed moderatley severe slowing. The proband's father was deceased but had a history of epileptic seizures.
07 Nov 2019	Early onset or syndromic epilepsy v1.399	DNAJC5	Rebecca Foulger commented on gene: DNAJC5: PMID:22978711: Cadieux-Dion et al., 2013. report a p.L116del variant in DNAJC5 in two distinct American families, and a p.L115R variant in an additional family. All individuals showed generalized tonic-clonic seizures.
07 Nov 2019	Early onset or syndromic epilepsy v1.399	DNAJC5	Rebecca Foulger gene: DNAJC5 was added gene: DNAJC5 was added to Genetic epilepsy syndromes. Sources: Literature,Other Mode of inheritance for gene: DNAJC5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: DNAJC5 were set to 22978711; 29506599; 22235333 Phenotypes for gene: DNAJC5 were set to Ceroid lipofuscinosis, neuronal, 4, Parry type, 162350; autosomal dominant Kufs disease; generalized tonic–clonic seizures Added comment: Added DNAJC5 to the Epilepsy panel based on a Green rating on the 'Inborn errors of metabolism' panel: seizures are listed as a symptom of MIM:162350 in OMIM. Sources: Literature, Other
28 Oct 2019	Early onset or syndromic epilepsy v1.398	CLN6	Rebecca Foulger commented on gene: CLN6: PMID:30561534. Berkovic et al., 2019 report phenotypes of patients with CLN6 pathogenic variants from 13 unrelated families (homozygous in 4 families and compound het in 9 families). The typical presentation was progressive myoclonus epilepsy with debilitating myoclonic seizures and relatively infrequent tonic-clonic seizures.
28 Oct 2019	Early onset or syndromic epilepsy v1.398	CLN6	Rebecca Foulger Publications for gene: CLN6 were set to 21549341; 31029456; 31216804
28 Oct 2019	Early onset or syndromic epilepsy v1.397	SETD5	Rebecca Foulger Phenotypes for gene: SETD5 were changed from Mental retardation, autosomal dominant 23 to Mental retardation, autosomal dominant 23, 615761
28 Oct 2019	Early onset or syndromic epilepsy v1.396	SETD5	Rebecca Foulger Publications for gene: SETD5 were set to
28 Oct 2019	Early onset or syndromic epilepsy v1.395	CLN6	Rebecca Foulger Publications for gene: CLN6 were set to 21549341; 31029456
28 Oct 2019	Early onset or syndromic epilepsy v1.394	CLN6	Rebecca Foulger changed review comment from: PMID:31216804. Zhang et al. 2019 identify the pathogenic gene variants and clinical phenotype features of 26 children with progressive myoclonic epilepsy. 1 patient had a variant in CLN6 (full English text not avaialble).; to: PMID:31216804. Zhang et al. 2019 identify the pathogenic gene variants and clinical phenotype features of 26 children with progressive myoclonic epilepsy. 1 patient had a variant in CLN6 (full English text not available).
28 Oct 2019	Early onset or syndromic epilepsy v1.394	CLN6	Rebecca Foulger commented on gene: CLN6: PMID:31216804. Zhang et al. 2019 identify the pathogenic gene variants and clinical phenotype features of 26 children with progressive myoclonic epilepsy. 1 patient had a variant in CLN6 (full English text not avaialble).
28 Oct 2019	Early onset or syndromic epilepsy v1.394	CLN6	Rebecca Foulger commented on gene: CLN6: Additional case in PMID:31029456 (Matsumoto et al., 2019) of Japanese boy with a homozygous C.794_976del variant p. (Ser265del) in CLN6. Symptoms include focal seizures.
28 Oct 2019	Early onset or syndromic epilepsy v1.394	CLN6	Rebecca Foulger Publications for gene: CLN6 were set to 21549341
28 Oct 2019	Early onset or syndromic epilepsy v1.393	SGSH	Rebecca Foulger Classified gene: SGSH as Green List (high evidence)
28 Oct 2019	Early onset or syndromic epilepsy v1.393	SGSH	Rebecca Foulger Added comment: Comment on list classification: Added SGSH to the panel with a Green rating: Green on the 'Inborn errors of metabolism' panel, and seizures are part of the MPS IIIA phenotype. Sufficient cases from the literature for inclusion on the panel.
28 Oct 2019	Early onset or syndromic epilepsy v1.393	SGSH	Rebecca Foulger Gene: sgsh has been classified as Green List (High Evidence).
28 Oct 2019	Early onset or syndromic epilepsy v1.392	SGSH	Rebecca Foulger commented on gene: SGSH: PMID: 30593151 (Li et al., 2018) report an 8 year old female with developmental regression and seizures amongst her symptoms. She was diagnosed with autosomal recessive (AR) MPS IIIA with compound het variants in SGSH (c.1298G>A p.Arg433Gln and c.630 G>T p.Trp210Cys), inherited from each parent. The pathogenicity of c.630G>T has not been reported yet. c.1298G>A has been associated with MPS-IIIA previously.
28 Oct 2019	Early onset or syndromic epilepsy v1.392	SGSH	Rebecca Foulger commented on gene: SGSH: PMID:21061399: Valstar et al. 2010 retrospectively reviewed the clinical features of 92 patients with MPS IIIA, including 32 living and 60 deceased individuals. There was wide phenotypic variability but Epilepsy was reported in 53/80 patients with a median seizure age of 11 years (range, 1-43 years). Patients with a severe MPS IIIA phenotype developed epilepsy at a significantly earlier age compared to patients suffering from a more attenuated form of the disease.
28 Oct 2019	Early onset or syndromic epilepsy v1.392	SGSH	Rebecca Foulger gene: SGSH was added gene: SGSH was added to Genetic epilepsy syndromes. Sources: Literature,Other Mode of inheritance for gene: SGSH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SGSH were set to 21061399; 30593151 Phenotypes for gene: SGSH were set to Mucopolysaccharidosis type IIIA (Sanfilippo A), 252900; seizures Review for gene: SGSH was set to GREEN Added comment: Added SGSH to the panel based on Green rating on the 'Inborn errors of metabolism' panel: seizures are a part of the Mucopolysaccharidosis phenotype. Sources: Literature, Other
24 Oct 2019	Early onset or syndromic epilepsy v1.391		Rebecca Foulger Panel types changed to Rare Disease 100K; GMS Rare Disease
24 Oct 2019	Early onset or syndromic epilepsy v1.389		Rebecca Foulger List of related panels changed from Epilepsy Plus; Epilepsy plus other features; Genetic Epilepsy Syndromes; Epileptic encephalopathy; Familial Focal Epilepsies; Familial Genetic Generalised Epilepsies; Genetic Epilepsies with Febrile Seizures Plus (GEFS+); Genetic Epilepsies with Febrile Seizures Plus to Epilepsy Plus; Epilepsy plus other features; Genetic Epilepsy Syndromes; Epileptic encephalopathy; Familial Focal Epilepsies; Familial Genetic Generalised Epilepsies; Genetic Epilepsies with Febrile Seizures Plus (GEFS+); Genetic Epilepsies with Febrile Seizures Plus; Early onset or syndromic epilepsy
24 Oct 2019	Early onset or syndromic epilepsy v1.388	APC2	Catherine Snow reviewed gene: APC2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
24 Oct 2019	Early onset or syndromic epilepsy v1.388	BSCL2	Rebecca Foulger Phenotypes for gene: BSCL2 were changed from Encephalopathy, progressive, with or without lipodystrophy 615924; Lipodystrophy, congenital generalized, type 2 269700; Neuropathy, distal hereditary motor, type VA 600794; Silver spastic paraplegia syndrome 270685 to Intractable epilepsy and neurological regression; Encephalopathy, progressive, with or without lipodystrophy 615924; Lipodystrophy, congenital generalized, type 2 269700; Neuropathy, distal hereditary motor, type VA 600794; Silver spastic paraplegia syndrome 270685
24 Oct 2019	Early onset or syndromic epilepsy v1.387	BSCL2	Rebecca Foulger Publications for gene: BSCL2 were set to 24896178; 26503795; 23564749; 15181077; 30767895; 23564749
24 Oct 2019	Early onset or syndromic epilepsy v1.386	BSCL2	Rebecca Foulger Added comment: Comment on mode of inheritance: PMID:31369919 (Fernandez-Marmiesse et al., 2019) report 2 siblings with profound refractory epilepsy and neurological regression. A de novo Met189Lys variant in BSCL2 was detected that was absent in the parents and unaffected sibling. This is the first evidence of an association between a heterozygous BSCL2 variant and EIEE, and supports an AD+AR Mode of inheritance.
24 Oct 2019	Early onset or syndromic epilepsy v1.386	BSCL2	Rebecca Foulger Mode of inheritance for gene: BSCL2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
24 Oct 2019	Early onset or syndromic epilepsy v1.385	BSCL2	Rebecca Foulger Publications for gene: BSCL2 were set to 24896178; 26503795; 23564749; 15181077; 30767895
24 Oct 2019	Early onset or syndromic epilepsy v1.384	CYP27A1	Rebecca Foulger Publications for gene: CYP27A1 were set to 18227423; 22336472; 24442603; 29484516
24 Oct 2019	Early onset or syndromic epilepsy v1.383	EXT2	Rebecca Foulger changed review comment from: Comment on list classification: Added CLPB to panel based on epilepsy/seizure phenotype on the 'Inborn errors of metabolism' panel. Relevant phenotype (MIM:616682) and sufficient cases of patients with seizures for inclusion on the panel: (PMIDs 26246518, 30075207, 30997052, 30288735).; to: Comment on list classification: Added EXT2 to panel based on epilepsy/seizure phenotype on the 'Inborn errors of metabolism' panel. Relevant phenotype (MIM:616682) and sufficient cases of patients with seizures for inclusion on the panel: (PMIDs 26246518, 30075207, 30997052, 30288735).
24 Oct 2019	Early onset or syndromic epilepsy v1.383	EMX2	Rebecca Foulger Classified gene: EMX2 as Amber List (moderate evidence)
24 Oct 2019	Early onset or syndromic epilepsy v1.383	EMX2	Rebecca Foulger Gene: emx2 has been classified as Amber List (Moderate Evidence).
24 Oct 2019	Early onset or syndromic epilepsy v1.382	EMX2	Rebecca Foulger Classified gene: EMX2 as Green List (high evidence)
24 Oct 2019	Early onset or syndromic epilepsy v1.382	EMX2	Rebecca Foulger Added comment: Comment on list classification: Demoted EMX2 from Green to Amber based on the Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy, and the post-Webex review by Helen Lord. The Schizencephaly phenotype is more appropriate for the ID/Cortical malformations panel, and EMX2 has now been added as a Green gene to 'Malformations of cortical development' (#96) panel.
24 Oct 2019	Early onset or syndromic epilepsy v1.382	EMX2	Rebecca Foulger Gene: emx2 has been classified as Green List (High Evidence).
24 Oct 2019	Early onset or syndromic epilepsy v1.381	TDP2	Catherine Snow changed review comment from: Comment on list classification: TDP2 is in OMIM with a relevant clinical features but not in Gene2Phenotype. TDP2 was identified by Konstantinos Varvagiannis who reviewed all variants. Sufficient number of individuals from unrelated families reported upon in the literature and three different variants identified. Therefore TDP2 can be classified as Green; to: Comment on list classification: TDP2 is in OMIM with a relevant clinical features but not in Gene2Phenotype. TDP2 was identified by Konstantinos Varvagiannis who reviewed all variants. All individuals reported to have seizures, although age of onset varied from 2 months to 12 years. There are sufficient number of individuals from unrelated families reported upon in the literature and three different variants identified. Therefore TDP2 can be classified as Green.
24 Oct 2019	Early onset or syndromic epilepsy v1.381	TDP2	Catherine Snow Classified gene: TDP2 as Green List (high evidence)
24 Oct 2019	Early onset or syndromic epilepsy v1.381	TDP2	Catherine Snow Added comment: Comment on list classification: TDP2 is in OMIM with a relevant clinical features but not in Gene2Phenotype. TDP2 was identified by Konstantinos Varvagiannis who reviewed all variants. Sufficient number of individuals from unrelated families reported upon in the literature and three different variants identified. Therefore TDP2 can be classified as Green
24 Oct 2019	Early onset or syndromic epilepsy v1.381	TDP2	Catherine Snow Gene: tdp2 has been classified as Green List (High Evidence).
24 Oct 2019	Early onset or syndromic epilepsy v1.380	TDP2	Catherine Snow Mode of inheritance for gene: TDP2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
24 Oct 2019	Early onset or syndromic epilepsy v1.379	TANC2	Rebecca Foulger Classified gene: TANC2 as Amber List (moderate evidence)
24 Oct 2019	Early onset or syndromic epilepsy v1.379	TANC2	Rebecca Foulger Added comment: Comment on list classification: Set rating of TANC2 to Amber. Not yet associated with a disorder in OMIM or Gene2Phenotype. One 2019 paper linking TANC2 with epilepsy in 11/20 cases: sufficient unrelated cases in PMID:31616000 but the pathogenicity of the variants has not been confirmed.
24 Oct 2019	Early onset or syndromic epilepsy v1.379	TANC2	Rebecca Foulger Gene: tanc2 has been classified as Amber List (Moderate Evidence).
24 Oct 2019	Early onset or syndromic epilepsy v1.378	TANC2	Rebecca Foulger gene: TANC2 was added gene: TANC2 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: TANC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TANC2 were set to 31616000 Phenotypes for gene: TANC2 were set to NDD syndrome; Neurodevelopmental Disorder; Intellectual disability; Seizures; Epilepsy Added comment: Added TANC2 to panel following curation of TANC2 on the Intellectual disability panel. PMID:31616000 (Guo et al, 2019) report 11/20 individuals with a TANC2 variant who had a formal diagnosis of epilepsy (n=9) or who suffered recurrent seizures (n=2). Sources: Literature
22 Oct 2019	Early onset or syndromic epilepsy v1.377	CLN6	Rebecca Foulger Classified gene: CLN6 as Amber List (moderate evidence)
22 Oct 2019	Early onset or syndromic epilepsy v1.377	CLN6	Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber based on Amber review by Tracy Lester and PMID:21549341 (Arsov et al., 2011) where seizures are a consistent feature across families.
22 Oct 2019	Early onset or syndromic epilepsy v1.377	CLN6	Rebecca Foulger Gene: cln6 has been classified as Amber List (Moderate Evidence).
21 Oct 2019	Early onset or syndromic epilepsy v1.376	NDUFS7	Rebecca Foulger Phenotypes for gene: NDUFS7 were changed from to Mitochondrial complex I deficiency, nuclear type 3, 618224
21 Oct 2019	Early onset or syndromic epilepsy v1.375	CLN6	Rebecca Foulger Mode of inheritance for gene: CLN6 was changed from to BIALLELIC, autosomal or pseudoautosomal
21 Oct 2019	Early onset or syndromic epilepsy v1.374	CLN6	Rebecca Foulger Publications for gene: CLN6 were set to
21 Oct 2019	Early onset or syndromic epilepsy v1.373	ALG2	Rebecca Foulger Phenotypes for gene: ALG2 were changed from to ?Congenital disorder of glycosylation type Ii, 607906; Myasthenic syndrome congenital 14 with tubular aggregates, 616228
21 Oct 2019	Early onset or syndromic epilepsy v1.372	ALG2	Rebecca Foulger Mode of inheritance for gene: ALG2 was changed from to BIALLELIC, autosomal or pseudoautosomal
21 Oct 2019	Early onset or syndromic epilepsy v1.371	EXT2	Rebecca Foulger changed review comment from: Comment on list classification: Relevant phenotype (MIM:616682) and sufficient cases of patients with seizures for inclusion on the panel: (PMIDs 26246518, 30075207, 30997052, 30288735).; to: Comment on list classification: Added CLPB to panel based on epilepsy/seizure phenotype on the 'Inborn errors of metabolism' panel. Relevant phenotype (MIM:616682) and sufficient cases of patients with seizures for inclusion on the panel: (PMIDs 26246518, 30075207, 30997052, 30288735).
21 Oct 2019	Early onset or syndromic epilepsy v1.371	TXN2	Rebecca Foulger commented on gene: TXN2
21 Oct 2019	Early onset or syndromic epilepsy v1.371	MT-CO3	Rebecca Foulger commented on gene: MT-CO3
21 Oct 2019	Early onset or syndromic epilepsy v1.371	EXT2	Rebecca Foulger Classified gene: EXT2 as Green List (high evidence)
21 Oct 2019	Early onset or syndromic epilepsy v1.371	EXT2	Rebecca Foulger Added comment: Comment on list classification: Relevant phenotype (MIM:616682) and sufficient cases of patients with seizures for inclusion on the panel: (PMIDs 26246518, 30075207, 30997052, 30288735).
21 Oct 2019	Early onset or syndromic epilepsy v1.371	EXT2	Rebecca Foulger Gene: ext2 has been classified as Green List (High Evidence).
21 Oct 2019	Early onset or syndromic epilepsy v1.370	CLPB	Rebecca Foulger commented on gene: CLPB
21 Oct 2019	Early onset or syndromic epilepsy v1.370	TXN2	Rebecca Foulger gene: TXN2 was added gene: TXN2 was added to Genetic epilepsy syndromes. Sources: Literature,Expert Review Red Mode of inheritance for gene: TXN2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TXN2 were set to 26626369 Phenotypes for gene: TXN2 were set to ?Combined oxidative phosphorylation deficiency 29, 616811; infantile-onset neurodegenerative disorder with severe cerebellar atrophy, epilepsy, dystonia, optic atrophy, and peripheral neuropathy
21 Oct 2019	Early onset or syndromic epilepsy v1.370	MT-CO3	Rebecca Foulger gene: MT-CO3 was added gene: MT-CO3 was added to Genetic epilepsy syndromes. Sources: Literature,Expert Review Red Mode of inheritance for gene gene: MT-CO3 was set to MITOCHONDRIAL Publications for gene: MT-CO3 were set to 8739943; 12915481 Phenotypes for gene: MT-CO3 were set to seizures
21 Oct 2019	Early onset or syndromic epilepsy v1.370	EXT2	Rebecca Foulger gene: EXT2 was added gene: EXT2 was added to Genetic epilepsy syndromes. Sources: Literature,Expert Review Green Mode of inheritance for gene: EXT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EXT2 were set to 26246518; 30997052; 30288735; 30075207 Phenotypes for gene: EXT2 were set to Seizures, scoliosis, and macrocephaly syndrome, 616682
21 Oct 2019	Early onset or syndromic epilepsy v1.370	CLPB	Rebecca Foulger gene: CLPB was added gene: CLPB was added to Genetic epilepsy syndromes. Sources: Literature,Expert Review Green Mode of inheritance for gene: CLPB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CLPB were set to 26916670; 25597510; 25597511 Phenotypes for gene: CLPB were set to Seizures; Generalised epilepsy; 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, 616271
21 Oct 2019	Early onset or syndromic epilepsy v1.369	GPHN	Rebecca Foulger Publications for gene: GPHN were set to 26613940; 12684523; 11095995; 22040219; 24561070
21 Oct 2019	Early onset or syndromic epilepsy v1.368	GPHN	Rebecca Foulger Added comment: Comment on mode of inheritance: Updated MOI from BIALLELIC to BOTH monoallelic and biallelic. Although OMIM records AR inheritance, a review by Tracy Lester notes PMIDs:24561070, 23393157 who report the association of hemizygous GPHN microdeletions with an epilepsy phenotype. The biallelic and monoallelic MOI matches the MOI of GPHN on the metabolism panels.
21 Oct 2019	Early onset or syndromic epilepsy v1.368	GPHN	Rebecca Foulger Mode of inheritance for gene: GPHN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
21 Oct 2019	Early onset or syndromic epilepsy v1.367	GPHN	Rebecca Foulger Publications for gene: GPHN were set to 26613940; 12684523; 11095995
21 Oct 2019	Early onset or syndromic epilepsy v1.366	ABAT	Rebecca Foulger Publications for gene: ABAT were set to 20052547; 27376954
14 Oct 2019	Early onset or syndromic epilepsy v1.365	ADAR	Rebecca Foulger Publications for gene: ADAR were set to
14 Oct 2019	Early onset or syndromic epilepsy v1.364	KCNJ11	Rebecca Foulger changed review comment from: Comment on mode of inheritance: Most KCNJ11 seizure patients have heterozygous variants but PMID:27181099 report a patient with a homozygous variant in KCNJ11 (p.F315I) and congenital hyperinsulinism. The authors say the patient had severe hypoglycemia and seizure following birth, but no further seizure details are given. OMIM disorder 'Diabetes, permanent neonatal, with or without neurologic features (MIM:606176) has both AR and AD inheritance recorded. Therefore based on PMID:27181099 plus OMIM plu review by West Midlands, Oxford and Wessex GLH, have updated MOI from 'monoallelic' to 'BOTH monoallelic and biallelic'.; to: Comment on mode of inheritance: Most KCNJ11 seizure patients have heterozygous variants but PMID:27181099 report a patient with a homozygous variant in KCNJ11 (p.F315I) and congenital hyperinsulinism. The authors say the patient had severe hypoglycemia and seizure following birth, but no further seizure details are given. OMIM disorder 'Diabetes, permanent neonatal, with or without neurologic features (MIM:606176) has both AR and AD inheritance recorded. Therefore based on PMID:27181099 plus OMIM plus review by West Midlands, Oxford and Wessex GLH, have updated MOI from 'monoallelic' to 'BOTH monoallelic and biallelic'.
14 Oct 2019	Early onset or syndromic epilepsy v1.364	ISCA-37446-Loss	Rebecca Foulger commented on Region: ISCA-37446-Loss: PMID:30977115: Eaton et al., 2019: Overall, 11% (12/108) of deletion carriers had an epilepsy diagnosis. 57/96 remaining deletion carriers (59.4%) had seizures or seizure-like symptoms (including febrile seizures). Most patients with 22q11.2 deletion syndrome had either deletion type A-D (ISCA-37446 75.9%) or deletion type A-B (ISCA-37433 6.5% 7/108 patients)- see Table 1.
14 Oct 2019	Early onset or syndromic epilepsy v1.364	ISCA-37446-Loss	Rebecca Foulger commented on Region: ISCA-37446-Loss: Added CNV to panel on recommendation from Alisdair McNeill (SHEFFIELD CHILDREN'S NHS FOUNDATION TRUST) who notes that "Multiple case series demonstrate 22q11.2 deletion syndrome is associated with epilepsy, e.g. PubMed:30977115" (personal communication via email, October 7th 2019).
14 Oct 2019	Early onset or syndromic epilepsy v1.364	ISCA-37433-Loss	Rebecca Foulger commented on Region: ISCA-37433-Loss: PMID:30977115: Eaton et al., 2019: Overall, 11% (12/108) of deletion carriers had an epilepsy diagnosis. 57/96 remaining deletion carriers (59.4%) had seizures or seizure-like symptoms (including febrile seizures). Most patients with 22q11.2 deletion syndrome had either deletion type A-D (ISCA-37446 75.9%) or deletion type A-B (ISCA-37433 6.5% 7/108 patients)- see Table 1.
14 Oct 2019	Early onset or syndromic epilepsy v1.364	ISCA-37433-Loss	Rebecca Foulger commented on Region: ISCA-37433-Loss: Added CNV to panel on recommendation from Alisdair McNeill (SHEFFIELD CHILDREN'S NHS FOUNDATION TRUST) who notes that "Multiple case series demonstrate 22q11.2 deletion syndrome is associated with epilepsy, e.g. PubMed:30977115" (personal communication via email, October 7th 2019).
14 Oct 2019	Early onset or syndromic epilepsy v1.364	ISCA-37433-Loss	Rebecca Foulger reviewed Region: ISCA-37433-Loss: Rating: ; Mode of pathogenicity: None; Publications: 30977115; Phenotypes: Epilepsy, seizures, seizure-like symptoms; Mode of inheritance: None
14 Oct 2019	Early onset or syndromic epilepsy v1.364	ISCA-37446-Loss	Rebecca Foulger reviewed Region: ISCA-37446-Loss: Rating: ; Mode of pathogenicity: None; Publications: 30977115; Phenotypes: Epilepsy, seizures, seizure-like symptoms; Mode of inheritance: None
14 Oct 2019	Early onset or syndromic epilepsy v1.364	ISCA-37433-Loss	Rebecca Foulger Region: ISCA-37433-Loss was added Region: ISCA-37433-Loss was added to Genetic epilepsy syndromes. Sources: ClinGen,Expert Review Green Mode of inheritance for Region: ISCA-37433-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for Region: ISCA-37433-Loss were set to 15545748; 15889418; 20301696 Phenotypes for Region: ISCA-37433-Loss were set to Learning difficulties; immune deficiency; renal anomalies; cleft palate, polydactyly; 22q11.2 deletion syndrome; diaphragmatic hernia; 192430; polyhydramnios; DiGeorge syndrome; Velocardiofacial syndrome; 188400; facial dysmorphic features, high frequency of cardiac defects, including conotruncal defects, prematurity, growth restriction, microcephaly, and mild developmental delay; congenital heart disease
14 Oct 2019	Early onset or syndromic epilepsy v1.364	ISCA-37446-Loss	Rebecca Foulger Region: ISCA-37446-Loss was added Region: ISCA-37446-Loss was added to Genetic epilepsy syndromes. Sources: ClinGen,Expert Review Green Mode of inheritance for Region: ISCA-37446-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for Region: ISCA-37446-Loss were set to micrognathia; neonatal hypocalcemia, which may present as tetany or seizures, due to hypoplasia of the parathyroid glands, and susceptibility to infection due to a deficit of T cells; clefting; DiGeorge syndrome; Velocardiofacial syndrome; 188400; cardiac malformations; Hearing deficits
08 Oct 2019	Early onset or syndromic epilepsy v1.363	NDUFAF4	Rebecca Foulger commented on gene: NDUFAF4: Amber ratings from Tracy Lester and Zornitza Stark support the current Amber rating of NDUFAF4.
08 Oct 2019	Early onset or syndromic epilepsy v1.363	NDUFAF4	Rebecca Foulger Publications for gene: NDUFAF4 were set to
08 Oct 2019	Early onset or syndromic epilepsy v1.362	NDUFAF4	Rebecca Foulger Phenotypes for gene: NDUFAF4 were changed from to Mitochondrial complex I deficiency, nuclear type 15, 618237
08 Oct 2019	Early onset or syndromic epilepsy v1.361	NDUFAF4	Rebecca Foulger Mode of inheritance for gene: NDUFAF4 was changed from to BIALLELIC, autosomal or pseudoautosomal
08 Oct 2019	Early onset or syndromic epilepsy v1.360	CCND2	Rebecca Foulger Marked gene: CCND2 as ready
08 Oct 2019	Early onset or syndromic epilepsy v1.360	CCND2	Rebecca Foulger Gene: ccnd2 has been classified as Red List (Low Evidence).
08 Oct 2019	Early onset or syndromic epilepsy v1.360	CCND2	Rebecca Foulger Classified gene: CCND2 as Red List (low evidence)
08 Oct 2019	Early onset or syndromic epilepsy v1.360	CCND2	Rebecca Foulger Added comment: Comment on list classification: Demoted CCND2 from Amber to Red following Red reviews by Zornitza Stark and Tracy Lester- as noted previously by Sarah Leigh: epilepsy is not a reported feature of the disorder.
08 Oct 2019	Early onset or syndromic epilepsy v1.360	CCND2	Rebecca Foulger Gene: ccnd2 has been classified as Red List (Low Evidence).
08 Oct 2019	Early onset or syndromic epilepsy v1.359	CCND2	Rebecca Foulger Mode of inheritance for gene: CCND2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
08 Oct 2019	Early onset or syndromic epilepsy v1.358	CCND2	Rebecca Foulger Publications for gene: CCND2 were set to
08 Oct 2019	Early onset or syndromic epilepsy v1.357	CCND2	Rebecca Foulger Phenotypes for gene: CCND2 were changed from to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3, 615938
08 Oct 2019	Early onset or syndromic epilepsy v1.356	ARID1B	Rebecca Foulger Marked gene: ARID1B as ready
08 Oct 2019	Early onset or syndromic epilepsy v1.356	ARID1B	Rebecca Foulger Gene: arid1b has been classified as Green List (High Evidence).
08 Oct 2019	Early onset or syndromic epilepsy v1.356	ARID1B	Rebecca Foulger commented on gene: ARID1B: The Green rating by Dr Alisdair McNeil (Sheffield Children's Hospital, Yorkshire and North East GLH) supports the current Green rating of ARID1B.
08 Oct 2019	Early onset or syndromic epilepsy v1.356	ARID1B	Rebecca Foulger Publications for gene: ARID1B were set to
08 Oct 2019	Early onset or syndromic epilepsy v1.355	ASAH1	Rebecca Foulger Marked gene: ASAH1 as ready
08 Oct 2019	Early onset or syndromic epilepsy v1.355	ASAH1	Rebecca Foulger Gene: asah1 has been classified as Green List (High Evidence).
08 Oct 2019	Early onset or syndromic epilepsy v1.355	ASAH1	Rebecca Foulger commented on gene: ASAH1: The Green rating by Dr Alisdair McNeil (Sheffield Children's Hospital, Yorkshire and North East GLH) supports the current Green rating of ASAH1.
08 Oct 2019	Early onset or syndromic epilepsy v1.355	ASAH1	Rebecca Foulger Phenotypes for gene: ASAH1 were changed from Spinal muscular atrophy with progressive myoclonic epilepsy, 159950 to Spinal muscular atrophy with progressive myoclonic epilepsy, 159950; SMA with myoclonic epilepsy
08 Oct 2019	Early onset or syndromic epilepsy v1.354	ASAH1	Rebecca Foulger Publications for gene: ASAH1 were set to 8955159; 22703880; 29169047; 24164096; 30291339; 27026573; 29169047; 30291339; 27026573; 26526000; 25578555; 31216804; 27723502
08 Oct 2019	Early onset or syndromic epilepsy v1.354	ASAH1	Rebecca Foulger Publications for gene: ASAH1 were set to 29169047; 22703880; 24164096; 30291339; 27026573; 29169047; 30291339; 27026573; 26526000; 25578555; 31216804; 27723502
08 Oct 2019	Early onset or syndromic epilepsy v1.353	ISCA-37429-Loss	Rebecca Foulger changed review comment from: The Green rating by Alisdair McNeil (Sheffield Children's Hospital, Yorkshire and North East GLH) supports the current Green rating of ISCA-37429-Loss CNV.; to: The Green rating by Alisdair McNeill (Sheffield Children's Hospital, Yorkshire and North East GLH) supports the current Green rating of ISCA-37429-Loss CNV.
08 Oct 2019	Early onset or syndromic epilepsy v1.353	CREBBP	Rebecca Foulger Added comment: Comment on mode of inheritance: Changed MOI from 'imprinted status unknown' to 'NOT imprinted' to match reviews from GLH experts Tracy Lester and Alisdair McNeill.
08 Oct 2019	Early onset or syndromic epilepsy v1.353	CREBBP	Rebecca Foulger Mode of inheritance for gene: CREBBP was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
08 Oct 2019	Early onset or syndromic epilepsy v1.352	CREBBP	Rebecca Foulger commented on gene: CREBBP: The Green rating by Dr Alisdair McNeill (Sheffield Children's Hospital, Yorkshire and North East GLH) supports the current Green rating of CREBBP.
08 Oct 2019	Early onset or syndromic epilepsy v1.352	ISCA-37429-Loss	Rebecca Foulger Marked Region: ISCA-37429-Loss as ready
08 Oct 2019	Early onset or syndromic epilepsy v1.352	ISCA-37429-Loss	Rebecca Foulger Region: isca-37429-loss has been classified as Green List (High Evidence).
08 Oct 2019	Early onset or syndromic epilepsy v1.352	ISCA-37429-Loss	Rebecca Foulger commented on Region: ISCA-37429-Loss: The Green rating by Alisdair McNeil (Sheffield Children's Hospital, Yorkshire and North East GLH) supports the current Green rating of ISCA-37429-Loss CNV.
07 Oct 2019	Early onset or syndromic epilepsy v1.352	ISCA-37429-Loss	alisdair mcneill reviewed Region: ISCA-37429-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
07 Oct 2019	Early onset or syndromic epilepsy v1.352	FLNA	alisdair mcneill reviewed gene: FLNA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
07 Oct 2019	Early onset or syndromic epilepsy v1.352	CREBBP	alisdair mcneill reviewed gene: CREBBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 29460469; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
07 Oct 2019	Early onset or syndromic epilepsy v1.352	ASAH1	alisdair mcneill reviewed gene: ASAH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: SMA with myoclonic epilepsy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
07 Oct 2019	Early onset or syndromic epilepsy v1.352	ARID1B	alisdair mcneill reviewed gene: ARID1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
07 Oct 2019	Early onset or syndromic epilepsy v1.352	KCNA1	Rebecca Foulger Publications for gene: KCNA1 were set to 29056246; 11026449; 9581771
07 Oct 2019	Early onset or syndromic epilepsy v1.351	KCNA1	Rebecca Foulger edited their review of gene: KCNA1: Added comment: Added a Red review to highlight the comment from Diane Cairns (Manchester University NHS, North West GLH) that it would be acceptable to remove this gene from the Epilepsy Panel.; Changed rating: RED
07 Oct 2019	Early onset or syndromic epilepsy v1.351	SCN9A	Rebecca Foulger edited their review of gene: SCN9A: Added comment: Added a Red review to highlight the comment from Diane Cairns (Manchester University NHS, North West GLH) that it would be acceptable to remove this gene from the Epilepsy Panel.; Changed rating: RED
07 Oct 2019	Early onset or syndromic epilepsy v1.351	FLNA	Rebecca Foulger edited their review of gene: FLNA: Added comment: Added a Red review to highlight the comment from Diane Cairns (Manchester University NHS, North West GLH) that it would be acceptable to remove this gene from the Epilepsy Panel.; Changed rating: RED
06 Oct 2019	Early onset or syndromic epilepsy v1.351	TDP2	Konstantinos Varvagiannis gene: TDP2 was added gene: TDP2 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: TDP2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TDP2 were set to 24658003; 30109272; 31410782 Phenotypes for gene: TDP2 were set to Spinocerebellar ataxia, autosomal recessive 23, 616949 Penetrance for gene: TDP2 were set to unknown Review for gene: TDP2 was set to GREEN Added comment: Biallelic pathogenic TGP2 variants cause Spinocerebellar ataxia, autosomal recessive 23 (MIM 616949). At least 6 affected individuals from 4 families have been reported, in all cases homozygous for LoF variants (3 different). ID, epilepsy and ataxia are consistent features of the disorder. TDP2 encodes a phosphodiesterase that is required for efficient repair of double strand breaks (DSBs) produced by abortive topoisomerase II (TOP2) activity. The gene is expressed in fetal and adult human brain. Evidence at the variant level (mRNA, protein levels) and additional studies for impairment of TOP2-induced DSB repair support a role. Animal models (primarily mice) reproduce the DSB repair defect, provide some histopathological evidence, show transcriptional dysregulation of genes (in line with the role of TOP2 in transcription). They have however failed to reproduce relevant neurological phenotypes. Published studies are summarized below. TDP2 is included in gene panels for ID offered by some diagnostic laboratories (incl. Radboudumc and GeneDx). There is no associated phenotype in G2P. TDP2 is listed among the current primary ID genes in SysID. Overall, this gene could be considered for inclusion in the ID and epilepsy panels probably as green (>=3 patients/families/variants, relevant ID and seizures in all, expression in brain, mRNA/protein levels tested, impaired activity) or amber (absence of neurological phenotypes in mouse model). ------------ [1] - PMID: 24658003 (Gómez-Herreros et al. 2014): Reports 3 individuals from a consanguineous Irish family. Features included seizures (onset by 2m, 6m and 12y), ID (3/3) and ataxia (3/3). A splicing variant (NM_016614.3:c.425+1G>A) was found in a 9.08-Mb region of homozygosity shared by all. A further ZNF193 missense variant localizing in the same region was thought unlikely to contribute to the phenotype (evidence also provided in subsequent study). The effect of the specific variant was proven by abnormal mRNA size, lower mRNA levels due to NMD (corrected upon cyclohexamide treatment), loss of TDP2 protein upon WB, loss of protein activity in lymphoblastoid cells from affected individuals, decreased repair of DSBs and increased cell death upon addition of etoposide (which promotes TOP2 abortive activity). The authors report very briefly on a further patient (from Egypt), with ID, 'reports of fits' and ataxia. This individual, with also affected sibs, was homozygous LoF (c.413_414delinsAA / p.Ser138*). Again, the authors were not able to detect TDP2 activity in blood from this subject. As also commented: - TDP2 has relevant expression in human (particularly adult) brain. - Mouse model : Tdp2 is expressed in relevant tissues, absence of Tdp2 activity was observed in neural tissue of mice homoyzgous for an ex1-3 del, with impairment of DSB repair. The authors were unable to detect a neurological phenotype with behavioral analyses, preliminary assesment of seizure propensity. Mice did not show developmental defects. Histopathology however, revealed ~25% reduction in the density of interneurons in cerebellum (a 'hallmark of DSB repair' and associated with seizures and ataxia). Transcription of several genes was shown to be disregulated. - Knockdown in zebrafish appears to affect left-right axis detremination (cited PMID: 18039968). [2] - PMID: 30109272 (Zagnoli-Vieira et al. 2018): A 6 y.o. male with seizures (onset by 5m), hypotonia, DD and ID, microcephaly and some additional clinical features and testing (ETC studies on muscle biopsy, +lactate, +(lactate/pyruvate) ratio) which could be suggestive of mitochondrial disorder. This individual from the US was homozygous for the c.425+1G>A variant but lacked the ZNF193 one (despite a shared haplotype with the Irish patients). Again absence of the protein was shown upon WB in patient fibroblasts, also supported by its activity. Complementation studies restored the DSB repair defect. The defect was specific to TOP2-induced DSBs as suggested by hypersensitivity to etoposide but not to ionizing radiation. CRISPR/Cas9 generated mutant human A549 cells demonstrated abnormal DSB repair. Fibroblasts / edited A549 cells failed to show mitochondrial defects (which were noted in muscle). [3] - PMID: 31410782 (Ciaccio et al. 2019): A girl born to consanguineous Italian parents, presented with moderate/severe ID, seizures (onset at 12y) and - among others - gait ataxia, tremor and dysmetria. MRI at the age of 12, demonstrated cerebellar atrophy (although previous exams were N). WES revealed a homozygous nonsense variant (c.400C>T / p.Arg134Ter) for which each parent was found to be carrier. Previous investigations included aCGH, NGS testing for epilepsy and metabolic testing. Sources: Literature
06 Oct 2019	Early onset or syndromic epilepsy v1.351	APC2	Konstantinos Varvagiannis gene: APC2 was added gene: APC2 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: APC2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: APC2 were set to 31585108; 25753423; 19759310; 22573669 Phenotypes for gene: APC2 were set to Global developmental delay; Intellectual disability; Seizures; Abnormality of the eye; Abnormality of nervous system morphology; Hearing abnormality; Abnormality of the cardiovascular system; Abnormality of the skeletal system; Abnormality of the genitourinary system Penetrance for gene: APC2 were set to Complete Review for gene: APC2 was set to AMBER Added comment: This gene was reviewed for the ID panel (details below). It could be also be considered for inclusion in the epilepsy panel as amber/green. [Seizures in 8/14 individuals (generalized tonic-clonic/myoclonic, onset 3m - 6yrs) although some individuals were too young when last examined (eg. 8m) and sibs in one family (F7) were discordant for this feature at the ages of 4y7m (+) and 6y (-). Lissencephaly is often associated with seizures which have occasionally been observed in Apc2-deficient mice (PMID cited: 22573669)]. ----- Probably 14 individuals from 9 families (8 consanguineous) with biallelic APC2 LoF variants have been reported. ID and brain abnormalities were features in all, although the presentation was quite different between sibs in the first report (PMID: 25753423 - mild/mod ID, ventriculomegaly and CC anomalies, macrocephaly with variable height, Sotos-like facial features) and 12 subsequently described patients (PMID: 31585108 - severe ID, P>A lissencephaly/CC anomalies/ventriculomegaly/paucity of white matter in (almost) all, gT-C/myoclonic seizures in 8/12 with onset 3m-6y, OFC in the low percentiles). In all cases relevant alternative diagnoses (eg. macrocephaly/overgrowth syndromes - 1st report, mutations in other lissencephaly genes, metabolic disorders - 2nd) were ruled out. APC2 encodes Adenomatous polyposis coli protein 2, expressed in the CNS. All variants reported to date were LoF (stopgain/frameshift/splicing) and were supported by parental-only studies. Mutations in the 1st report as well as 4/8 variants from the 2nd report localized within the last exon (NM_005883.2 / longest of >=3 isoforms), although the 2nd report did not observe obvious genotype-phenotype correlations. Despite a pLI of 1 in gnomAD, Lee et al. comment that heterozygous carriers did not have any noticeable phenotype. They further note that carriers were not examined by brain MRI, though. 27 heterozygous high-confidence variants appear in individuals in gnomAD. Finally as commented on, APC2 is not mutated in colon cancer. Animal models: Apc -/- mice displayed disrupted neuronal migration, with defects of lamination of cerebral cortex and cerebellum supporting the observed brain abnormalities. In addition Apc2-deficient mice also presented impaired learning and memory abilities. Extensive additional studies have shown Apc2 co-localization with microtubules affecting their stabilization, distribution along actin fibers (all supporting a role in cytoskeletal organization) and regulation of Rac1 (a Rho GTPase). Generation of Neuro2a cells demonstrated abnormal localization mainly in cell bodies of mutant hAPC2 proteins (due to frameshift in the last exon / deletion of the C-terminal part) - different from wt (neurites, growth cones, cell bodies). The first patient report also provided evidence for Apc2 being a downstream effector of Nsd1, with Nsd1 knockdown brains displaying impaired migration / laminar positioning of cortical neurons (similar to Apc2-/- model) and rescued by forced expression of Apc2. In OMIM, the APC2-related phenotype is ?Sotos syndrome 3 (MIM 617169 - AR). G2P does not have any associated phenotype for this gene. Relevant articles: PMIDs: 19759310 and 22573669 (Shintani et al. 2009 & 2012) [mouse model] PMID: 25753423 (Almuriekhi et al. 2015) [2 individuals + mouse model] PMID: 31585108 (Lee et al. 2019) [12 individuals from 8 families] Sources: Literature
03 Oct 2019	Early onset or syndromic epilepsy v1.351	AP2M1	Rebecca Foulger Phenotypes for gene: AP2M1 were changed from Seizures; Ataxia; Generalized hypotonia; Intellectual disability; Global developmental delay; Autistic behavior to Intellectual developmental disorder 60 with seizures, 618587; Seizures; Ataxia; Generalized hypotonia; Intellectual disability; Global developmental delay; Autistic behavior
03 Oct 2019	Early onset or syndromic epilepsy v1.350	PIGU	Rebecca Foulger Phenotypes for gene: PIGU were changed from myoclonic seizures; focal myoclonic seizures; Global developmental delay; Intellectual disability; Seizures; Cerebral atrophy; Cerebellar hypoplasia; Scoliosis to Glycosylphosphatidylinositol biosynthesis defect 2, 618590; myoclonic seizures; focal myoclonic seizures; Global developmental delay; Intellectual disability; Seizures; Cerebral atrophy; Cerebellar hypoplasia; Scoliosis
03 Oct 2019	Early onset or syndromic epilepsy v1.349	PIGQ	Rebecca Foulger Phenotypes for gene: PIGQ were changed from Intractable seizures; developmental delay; optic atrophy; epilepsy; Ohtahara syndrome to Epileptic encephalopathy, early infantile, 77, 618548; Intractable seizures; developmental delay; optic atrophy; epilepsy; Ohtahara syndrome
03 Oct 2019	Early onset or syndromic epilepsy v1.348	PIGB	Rebecca Foulger Phenotypes for gene: PIGB were changed from Generalized hypotonia; Global developmental delay; Intellectual disability; Seizures; Hearing abnormality; Abnormality of vision; Elevated alkaline phosphatase; Abnormality of the head; Abnormality of the hand; Abnormality of the foot to Epileptic encephalopathy, early infantile, 80, 618580; Generalized hypotonia; Global developmental delay; Intellectual disability; Seizures; Hearing abnormality; Abnormality of vision; Elevated alkaline phosphatase; Abnormality of the head; Abnormality of the hand; Abnormality of the foot
03 Oct 2019	Early onset or syndromic epilepsy v1.347	ACTL6B	Rebecca Foulger commented on gene: ACTL6B: ACTL6B now has a 'confirmed' rating for 'EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE' in the DD panel of Gene2Phenotype (DDG2P update, 18/09/2019), supporting the Green rating of ACTL6B on this panel.
30 Sep 2019	Early onset or syndromic epilepsy v1.347	ALKBH8	Rebecca Foulger Classified gene: ALKBH8 as Amber List (moderate evidence)
30 Sep 2019	Early onset or syndromic epilepsy v1.347	ALKBH8	Rebecca Foulger Added comment: Comment on list classification: Demoted ALKBH8 from Green to Amber following review from Helen Lord on behalf of West Midlands, Oxford and Wessex GLH, and agreement from Richard Scott (Genomics England clinical team).
30 Sep 2019	Early onset or syndromic epilepsy v1.347	ALKBH8	Rebecca Foulger Gene: alkbh8 has been classified as Amber List (Moderate Evidence).
30 Sep 2019	Early onset or syndromic epilepsy v1.346	POLG2	Rebecca Foulger Phenotypes for gene: POLG2 were changed from Autosomal Recessive Epilepsy Family Without Ophthalmoplegia; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4, 610131 to Mitochondrial DNA depletion syndrome 16 (hepatic type), 618528; Autosomal Recessive Epilepsy Family Without Ophthalmoplegia; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4, 610131
30 Sep 2019	Early onset or syndromic epilepsy v1.345	POLG2	Rebecca Foulger Phenotypes for gene: POLG2 were changed from Autosomal Recessive Epilepsy Family Without Ophthalmoplegia to Autosomal Recessive Epilepsy Family Without Ophthalmoplegia; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4, 610131
30 Sep 2019	Early onset or syndromic epilepsy v1.344	POLG2	Rebecca Foulger Added comment: Comment on mode of inheritance: Kept rating as Amber to match Helen Lord's review, but changed MOI from biallelic to 'BOTH biallelic and monoallelic' since (as Helen Lord notes) Young et al 2011 (PMID:21555342) report 4/11 patients with seizures as part of their phenotype and heterozygous variants in POLG2.
30 Sep 2019	Early onset or syndromic epilepsy v1.344	POLG2	Rebecca Foulger Mode of inheritance for gene: POLG2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
30 Sep 2019	Early onset or syndromic epilepsy v1.343	PIGP	Rebecca Foulger Tag watchlist tag was added to gene: PIGP.
30 Sep 2019	Early onset or syndromic epilepsy v1.343	PIGP	Rebecca Foulger Classified gene: PIGP as Amber List (moderate evidence)
30 Sep 2019	Early onset or syndromic epilepsy v1.343	PIGP	Rebecca Foulger Added comment: Comment on list classification: PIGP was added to the panel and rated Green by Konstantinos Varvagiannis. Upgraded rating from Grey to Amber, and added watchlist tag, following review of literature and GLH-review by Helen Lord. Not yet associated with a disorder in Gene2Phenotype. 2 unrelated cases from the literature plus a third case from LOVD. Therefore Amber rating is appropriate.
30 Sep 2019	Early onset or syndromic epilepsy v1.343	PIGP	Rebecca Foulger Gene: pigp has been classified as Amber List (Moderate Evidence).
26 Sep 2019	Early onset or syndromic epilepsy v1.342	KATNB1	Rebecca Foulger Tag watchlist tag was added to gene: KATNB1.
26 Sep 2019	Early onset or syndromic epilepsy v1.342	PMPCB	Konstantinos Varvagiannis changed review comment from: Review from the ID panel: Biallelic pathogenic PMPCB variants cause, Multiple mitochondrial dysfunctions syndrome 6 (MIM 617954). 5 relevant individuals from 4 unrelated families (in one case consanguineous) have been reported by Vögtle et al. (2018 - PMID: 29576218). Onset of symptoms (eg. hypotonia) often preceded a period of developmental regression/stagnation which was common in all individuals and occurred within the first 2 years of life, usually following febrile illness. In all cases neurological features were severe (lack of ambulation/speech). Seizures were observed in 4 individuals from 3 families, with onset at the age of 11-24m. MRI images demonstrated T2 signal hyperintensities of the basal ganglia with cerebellar and cerebral atrophy in some. Deterioration with early death was reported on three occasions, though some years after symptom onset. Following exclusion of other diagnoses in some cases (eg. aCGH, epilepsy panel), WES identified biallelic PMPCB missense variants, supported by Sanger confirmation and segregation studies. The following variants were reported (NM_004279.2): - c.523C>T (p.Arg175Cys) in trans with c.601G>C (p.Ala201Pro) [Fam A and B] - c.524G>A (p.Arg175His) in trans with c.530T>G (p.Val177Gly) [Fam C] - c.1265T>C (p.Ile422Thr) in homozygous state [Fam D with 2 affected sibs] The gene encodes the catalytic (beta) subunit of the mitochondrial processing protease (MPP) which is responsible for the cleavage/maturation of nuclear-encoded mitochondrial precursor proteins after their import in mitochondria. The alpha subunit is encoded by PMPCA (green rating proposed for this panel). Extensive studies demonstrated (perhaps a better summary provided by OMIM): - Reduced PMPCB protein levels in mitochondria isolated from patient fibroblasts or patient-derived pluripotent stem cells. - Frataxin maturation was impaired with accumulation of the intermediate form and lower amounts of mature FXN, indicating decrease in MPP activity. - Analysis of the homologous Mas1 S. cerevisiae mutants was carried out, with the exception of Ile422Thr (corresponding to Mas1 - Ile398Thr), the introduction of which did not yield viable yiest strains. Homologous mutations led to a temperature-sensitive phenotype with accumulation of immature/unprocessed precursor proteins and decrease of mature/processed forms both in vivo or in organello (following isolation of mitochondria). Under conditions of heat stress, Mas1 mutations decreased biogenesis of Fe-S clusters. - Respiratory chain complexes I-III contain Fe-S clusters. In muscle biopsy from an affected individual, complex II activity was significantly reduced (although this was not the case in fibroblasts or liver biopsy). Dysfunction of mitochondrial and cytosolic Fe-S cluster-dependent enzymes (eg. aconitase) was also shown in muscle tissue. Regression/stagnation with seizures/non-achievement of milestones may justify testing for an ID / epilepsy gene panel. In addition, metabolic studies or mitochondrial respiratory chain complex studies were sometimes non-informative (lactate elevated in 3/5 subjects) or not carried out at all / in relevant tissues (muscle biopsy in 2 individuals, fibroblasts/liver biopsy did not demonstrate reduced complex activity when tested). PMPCB is included in the ID gene panel of Radboudumc, as well as the SysID database. The gene is included in the DD panel of G2P associated with "Neurodegeneration in Early Childhood" (disease confidence : probable). As a result, PMPCB can be considered for inclusion in both epilepsy and ID panels as green (or amber). Sources: Literature; to: Review from the ID panel: Biallelic pathogenic PMPCB variants cause, Multiple mitochondrial dysfunctions syndrome 6 (MIM 617954). 5 relevant individuals from 4 unrelated families (in one case consanguineous) have been reported by Vögtle et al. (2018 - PMID: 29576218). Onset of symptoms (eg. hypotonia) often preceded a period of developmental regression/stagnation which was common in all individuals and occurred within the first 2 years of life, usually following febrile illness. In all cases neurological features were severe (lack of ambulation/speech). Seizures were observed in 4 individuals from 3 families, with onset at the age of 11-24m. MRI images demonstrated T2 signal hyperintensities of the basal ganglia with cerebellar and cerebral atrophy in some. Deterioration with early death was reported on three occasions, though some years after symptom onset. Following exclusion of other diagnoses in some cases (eg. aCGH, epilepsy panel), WES identified biallelic PMPCB missense variants, supported by Sanger confirmation and segregation studies. The following variants were reported (NM_004279.2): - c.523C>T (p.Arg175Cys) in trans with c.601G>C (p.Ala201Pro) [Fam A and B] - c.524G>A (p.Arg175His) in trans with c.530T>G (p.Val177Gly) [Fam C] - c.1265T>C (p.Ile422Thr) in homozygous state [Fam D with 2 affected sibs] The gene encodes the catalytic (beta) subunit of the mitochondrial processing protease (MPP) which is responsible for the cleavage/maturation of nuclear-encoded mitochondrial precursor proteins after their import in mitochondria. The alpha subunit is encoded by PMPCA (green rating proposed for this panel). Extensive studies demonstrated (perhaps a better summary provided by OMIM): - Reduced PMPCB protein levels in mitochondria isolated from patient fibroblasts or patient-derived pluripotent stem cells. - Frataxin maturation was impaired with accumulation of the intermediate form and lower amounts of mature FXN, indicating decrease in MPP activity. - Analysis of the homologous Mas1 S. cerevisiae mutants was carried out, with the exception of Ile422Thr (corresponding to Mas1 - Ile398Thr), the introduction of which did not yield viable yeast strains. Homologous mutations led to a temperature-sensitive phenotype with accumulation of immature/unprocessed precursor proteins and decrease of mature/processed forms both in vivo or in organello (following isolation of mitochondria). Under conditions of heat stress, Mas1 mutations decreased biogenesis of Fe-S clusters. - Respiratory chain complexes I-III contain Fe-S clusters. In muscle biopsy from an affected individual, complex II activity was significantly reduced (although this was not the case in fibroblasts or liver biopsy). Dysfunction of mitochondrial and cytosolic Fe-S cluster-dependent enzymes (eg. aconitase) was also shown in muscle tissue. Regression/stagnation with seizures/non-achievement of milestones may justify testing for an ID / epilepsy gene panel. In addition, metabolic studies or mitochondrial respiratory chain complex studies were sometimes non-informative (lactate elevated in 3/5 subjects) or not carried out at all / in relevant tissues (muscle biopsy in 2 individuals, fibroblasts/liver biopsy did not demonstrate reduced complex activity when tested). PMPCB is included in the ID gene panel of Radboudumc, as well as the SysID database. The gene is included in the DD panel of G2P associated with "Neurodegeneration in Early Childhood" (disease confidence : probable). As a result, PMPCB can be considered for inclusion in both epilepsy and ID panels as green (or amber). Sources: Literature
26 Sep 2019	Early onset or syndromic epilepsy v1.342	POLG2	Rebecca Foulger Publications for gene: POLG2 were set to 31286721; 27592148; 30157269
26 Sep 2019	Early onset or syndromic epilepsy v1.341	SPATA5	Rebecca Foulger Classified gene: SPATA5 as Green List (high evidence)
26 Sep 2019	Early onset or syndromic epilepsy v1.341	SPATA5	Rebecca Foulger Added comment: Comment on list classification: The Green review by Helen Lord (September 23rd 2019) supports the existing Green rating of SPATA5.
26 Sep 2019	Early onset or syndromic epilepsy v1.341	SPATA5	Rebecca Foulger Gene: spata5 has been classified as Green List (High Evidence).
26 Sep 2019	Early onset or syndromic epilepsy v1.340	KATNB1	Rebecca Foulger Classified gene: KATNB1 as Amber List (moderate evidence)
26 Sep 2019	Early onset or syndromic epilepsy v1.340	KATNB1	Rebecca Foulger Added comment: Comment on list classification: Updated rating from Grey to Amber, and added watchlist tag: KATNB1 was added to the panel and rated Green by Konstantinos Varvagiannis. Not yet associated with a disorder in Gene2Phenotype. Linked to lissencephaly with microcephaly in OMIM. There are sufficient cases from from the literature to support inclusion on the epilepsy panel (PMIDs:25521378, 25521379, 26640080) but epilepsy is not a feature in all cases and a Red recent review was left by Helen Lord. Therefore rated Amber as other panels may be more appropriate.
26 Sep 2019	Early onset or syndromic epilepsy v1.340	KATNB1	Rebecca Foulger Gene: katnb1 has been classified as Amber List (Moderate Evidence).
26 Sep 2019	Early onset or syndromic epilepsy v1.339	GABRA5	Rebecca Foulger Classified gene: GABRA5 as Green List (high evidence)
26 Sep 2019	Early onset or syndromic epilepsy v1.339	GABRA5	Rebecca Foulger Added comment: Comment on list classification: Updated rating from Grey to Green: GABRA5 was added to the panel and rated Green by Konstantinos Varvagiannis. Not yet associated with a disorder in Gene2Phenotype but linked to EIEE-70 in OMIM, and there are three cases from 2 publications (PMIDs 29961870 and 31056671) of GABRA5 variants associated with early infantile epileptic encephalopathy for a diagnostic rating. A Green rating is supported by a recent review by Helen Lord.
26 Sep 2019	Early onset or syndromic epilepsy v1.339	GABRA5	Rebecca Foulger Gene: gabra5 has been classified as Green List (High Evidence).
26 Sep 2019	Early onset or syndromic epilepsy v1.338	GABRA2	Rebecca Foulger Classified gene: GABRA2 as Green List (high evidence)
26 Sep 2019	Early onset or syndromic epilepsy v1.338	GABRA2	Rebecca Foulger Added comment: Comment on list classification: Updated rating from Grey to Green: GABRA2 was added to the panel and rated Green by Konstantinos Varvagiannis. Not yet associated with a disorder in Gene2Phenotype but linked to EIEE-78 in OMIM, and there are sufficient cases from from the literature (PMIDs:29422393, 29961870, 31032849, https://doi.org/10.1101/678219) of GABRA2 variants associated with early infantile epileptic encephalopathy for a diagnostic rating. A Green rating is supported by a recent review by Helen Lord.
26 Sep 2019	Early onset or syndromic epilepsy v1.338	GABRA2	Rebecca Foulger Gene: gabra2 has been classified as Green List (High Evidence).
26 Sep 2019	Early onset or syndromic epilepsy v1.337	PAK1	Rebecca Foulger Marked gene: PAK1 as ready
26 Sep 2019	Early onset or syndromic epilepsy v1.337	PAK1	Rebecca Foulger Gene: pak1 has been classified as Green List (High Evidence).
26 Sep 2019	Early onset or syndromic epilepsy v1.337	PAK1	Rebecca Foulger Classified gene: PAK1 as Green List (high evidence)
26 Sep 2019	Early onset or syndromic epilepsy v1.337	PAK1	Rebecca Foulger Added comment: Comment on list classification: Updated PAK1 from Amber to Green: Subsequent to the 8th August Webex, Konstantinos Varvagiannis left a Green review of PAK1 on the Epilepsy panel based on an additional 2019 paper (Horn et al, PMID:31504246). Green rating is supported by a new review by Helen Lord.
26 Sep 2019	Early onset or syndromic epilepsy v1.337	PAK1	Rebecca Foulger Gene: pak1 has been classified as Green List (High Evidence).
26 Sep 2019	Early onset or syndromic epilepsy v1.336	GABRA2	Rebecca Foulger changed review comment from: Summary of evidence (see Konstantinos Varvagiannis' reviews for details): Sufficient cases in OMIM and the literature to associate GABRA2 with 'Epileptic encephalopathy, early infantile, 78, 618557'. PMID:29422393, Orenstein et al., 2018 report a male of unrelated Ashkenazi Jewish parents with EIEE-78 and poor cognitive development, and a de novo heterozygous variant in GABRA2 (N335H). Functional studies were not performed but the variant was absent in ExAC and gnomAD controls. PMID:29961870, Butler et al. 2018 report an 11 year old girls with EIEE-78 who had multiple seizures starting age 6 weeks, and a de novo heterozygous variant in GABRA2 (T292K). PMID:31032849, Maljevic et al., 2019 decribe 5 patients (3 sporadic cases and 2 siblings) with four novel de novo GABRA2 missense variants (Val284Ala, Leu291Val, Met263Thr, Phe325Leu). All patients had seizures (Table 1) with onset 1day - 17years. The siblings inherited the variant from a mosaic father. https://doi.org/10.1101/678219: Sanchis-Juan et al., 2019 identified a de novo missense variant in GABRA2 gene (Pro280Leu) in a 10 year old girl with EIEE and developmental delay.; to: Summary of evidence (see Konstantinos Varvagiannis' reviews for details): Sufficient cases in OMIM and the literature to associate GABRA2 with 'Epileptic encephalopathy, early infantile, 78, 618557'. PMID:29422393, Orenstein et al., 2018 report a male of unrelated Ashkenazi Jewish parents with EIEE-78 and poor cognitive development, and a de novo heterozygous variant in GABRA2 (N335H). Functional studies were not performed but the variant was absent in ExAC and gnomAD controls. PMID:29961870, Butler et al. 2018 report an 11 year old girl with EIEE-78 who had multiple seizures starting age 6 weeks, and a de novo heterozygous variant in GABRA2 (T292K). PMID:31032849, Maljevic et al., 2019 decribe 5 patients (3 sporadic cases and 2 siblings) with four novel de novo GABRA2 missense variants (Val284Ala, Leu291Val, Met263Thr, Phe325Leu). All patients had seizures (Table 1) with onset 1day - 17years. The siblings inherited the variant from a mosaic father. https://doi.org/10.1101/678219: Sanchis-Juan et al., 2019 identified a de novo missense variant in GABRA2 gene (Pro280Leu) in a 10 year old girl with EIEE and developmental delay.
26 Sep 2019	Early onset or syndromic epilepsy v1.336	KATNB1	Rebecca Foulger changed review comment from: KATNB1 was added to the panel and rated Grey by Konstantinos Varvagiannis. Summary of evidence is as follows (see Konstantinos Varvagiannis' review for details): 3 publications reporting patients with biallelic KATNB1 variants. The phenotype includes seizures in some, but not all cases: PMID:25521378. Mishra-Gorur et al. 2014 report 5 families with malformations of cortical development and homozygous KATNB1 variants. In many families homozygous variants in additional genes were also reported. Epilepsy was reported in 3/7 individuals (from 2 families): Supplementary Table S1). PMID:25521379. Hu et al., 2014 report 3 Middle Eastern families with microcephaly, Global DD and seizures, and 3 different homozygous variants in KATNB1. PMID:26640080. Yigit el al. 2016 report a homozygous acceptor splice-site intronic KATNB1 variant in a 5 year old Turkish girl born to consanguineous cousins, who presented with congenital microcephaly, lissencephaly, short stature, polysyndactyly, dental abnormalities and developmental delay. She developed seizures age 6 months.; to: KATNB1 was added to the panel and rated Green by Konstantinos Varvagiannis. Summary of evidence is as follows (see Konstantinos Varvagiannis' review for details): 3 publications reporting patients with biallelic KATNB1 variants. The phenotype includes seizures in some, but not all cases: PMID:25521378. Mishra-Gorur et al. 2014 report 5 families with malformations of cortical development and homozygous KATNB1 variants. In many families homozygous variants in additional genes were also reported. Epilepsy was reported in 3/7 individuals (from 2 families): Supplementary Table S1). PMID:25521379. Hu et al., 2014 report 3 Middle Eastern families with microcephaly, Global DD and seizures, and 3 different homozygous variants in KATNB1. PMID:26640080. Yigit el al. 2016 report a homozygous acceptor splice-site intronic KATNB1 variant in a 5 year old Turkish girl born to consanguineous cousins, who presented with congenital microcephaly, lissencephaly, short stature, polysyndactyly, dental abnormalities and developmental delay. She developed seizures age 6 months.
26 Sep 2019	Early onset or syndromic epilepsy v1.336	PMPCB	Konstantinos Varvagiannis gene: PMPCB was added gene: PMPCB was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: PMPCB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PMPCB were set to 29576218 Phenotypes for gene: PMPCB were set to Multiple mitochondrial dysfunctions syndrome 6, 617954 Penetrance for gene: PMPCB were set to Complete Review for gene: PMPCB was set to GREEN Added comment: Review from the ID panel: Biallelic pathogenic PMPCB variants cause, Multiple mitochondrial dysfunctions syndrome 6 (MIM 617954). 5 relevant individuals from 4 unrelated families (in one case consanguineous) have been reported by Vögtle et al. (2018 - PMID: 29576218). Onset of symptoms (eg. hypotonia) often preceded a period of developmental regression/stagnation which was common in all individuals and occurred within the first 2 years of life, usually following febrile illness. In all cases neurological features were severe (lack of ambulation/speech). Seizures were observed in 4 individuals from 3 families, with onset at the age of 11-24m. MRI images demonstrated T2 signal hyperintensities of the basal ganglia with cerebellar and cerebral atrophy in some. Deterioration with early death was reported on three occasions, though some years after symptom onset. Following exclusion of other diagnoses in some cases (eg. aCGH, epilepsy panel), WES identified biallelic PMPCB missense variants, supported by Sanger confirmation and segregation studies. The following variants were reported (NM_004279.2): - c.523C>T (p.Arg175Cys) in trans with c.601G>C (p.Ala201Pro) [Fam A and B] - c.524G>A (p.Arg175His) in trans with c.530T>G (p.Val177Gly) [Fam C] - c.1265T>C (p.Ile422Thr) in homozygous state [Fam D with 2 affected sibs] The gene encodes the catalytic (beta) subunit of the mitochondrial processing protease (MPP) which is responsible for the cleavage/maturation of nuclear-encoded mitochondrial precursor proteins after their import in mitochondria. The alpha subunit is encoded by PMPCA (green rating proposed for this panel). Extensive studies demonstrated (perhaps a better summary provided by OMIM): - Reduced PMPCB protein levels in mitochondria isolated from patient fibroblasts or patient-derived pluripotent stem cells. - Frataxin maturation was impaired with accumulation of the intermediate form and lower amounts of mature FXN, indicating decrease in MPP activity. - Analysis of the homologous Mas1 S. cerevisiae mutants was carried out, with the exception of Ile422Thr (corresponding to Mas1 - Ile398Thr), the introduction of which did not yield viable yiest strains. Homologous mutations led to a temperature-sensitive phenotype with accumulation of immature/unprocessed precursor proteins and decrease of mature/processed forms both in vivo or in organello (following isolation of mitochondria). Under conditions of heat stress, Mas1 mutations decreased biogenesis of Fe-S clusters. - Respiratory chain complexes I-III contain Fe-S clusters. In muscle biopsy from an affected individual, complex II activity was significantly reduced (although this was not the case in fibroblasts or liver biopsy). Dysfunction of mitochondrial and cytosolic Fe-S cluster-dependent enzymes (eg. aconitase) was also shown in muscle tissue. Regression/stagnation with seizures/non-achievement of milestones may justify testing for an ID / epilepsy gene panel. In addition, metabolic studies or mitochondrial respiratory chain complex studies were sometimes non-informative (lactate elevated in 3/5 subjects) or not carried out at all / in relevant tissues (muscle biopsy in 2 individuals, fibroblasts/liver biopsy did not demonstrate reduced complex activity when tested). PMPCB is included in the ID gene panel of Radboudumc, as well as the SysID database. The gene is included in the DD panel of G2P associated with "Neurodegeneration in Early Childhood" (disease confidence : probable). As a result, PMPCB can be considered for inclusion in both epilepsy and ID panels as green (or amber). Sources: Literature
23 Sep 2019	Early onset or syndromic epilepsy v1.336	PAK1	Helen Lord edited their review of gene: PAK1: Added comment: Horn et al paper 2019 (31504246). 4 unrelated patients with intellectual disability, macrocephaly and seizures had de novo het missense variants in the PAK1 gene using trio exome sequencing. 3/4 of the patients reported as having seizures/focal epilepsy. 1/4 had one typical febrile seizure (age not known). All 4 variants located in important domains and are likely to lead to a gain of function.; Changed rating: GREEN; Changed publications: 31504246
23 Sep 2019	Early onset or syndromic epilepsy v1.336	POLG2	Helen Lord reviewed gene: POLG2: Rating: AMBER; Mode of pathogenicity: None; Publications: 21555342, 27592148, 30157269, 31286721; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
23 Sep 2019	Early onset or syndromic epilepsy v1.336	SPATA5	Helen Lord reviewed gene: SPATA5: Rating: GREEN; Mode of pathogenicity: None; Publications: 26299366, 29343804; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
23 Sep 2019	Early onset or syndromic epilepsy v1.336	GOT2	Helen Lord reviewed gene: GOT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31422819; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
23 Sep 2019	Early onset or syndromic epilepsy v1.336	GABRA2	Helen Lord reviewed gene: GABRA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29422393, 31032849; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
23 Sep 2019	Early onset or syndromic epilepsy v1.336	GABRA5	Helen Lord reviewed gene: GABRA5: Rating: GREEN; Mode of pathogenicity: None; Publications: 29961870, 31056671, 30033060; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
23 Sep 2019	Early onset or syndromic epilepsy v1.336	HNRNPR	Helen Lord reviewed gene: HNRNPR: Rating: GREEN; Mode of pathogenicity: None; Publications: 26795593, 31079900; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
23 Sep 2019	Early onset or syndromic epilepsy v1.336	KATNB1	Helen Lord reviewed gene: KATNB1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
23 Sep 2019	Early onset or syndromic epilepsy v1.336	PIGP	Helen Lord reviewed gene: PIGP: Rating: AMBER; Mode of pathogenicity: None; Publications: 28334793, 31139695; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
22 Sep 2019	Early onset or syndromic epilepsy v1.336	TIMM50	Konstantinos Varvagiannis reviewed gene: TIMM50: Rating: GREEN; Mode of pathogenicity: None; Publications: 27573165, 30190335, 31058414, Serajee et al. (ASHG conference 2015 - abstract Nr. 2299T); Phenotypes: 3-methylglutaconic aciduria, type IX (MIM 617698); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
20 Sep 2019	Early onset or syndromic epilepsy v1.336	SLC25A12	Rebecca Foulger Publications for gene: SLC25A12 were set to 24515575; 19641205; 27290639; 26633542
19 Sep 2019	Early onset or syndromic epilepsy v1.335	GABRA5	Rebecca Foulger commented on gene: GABRA5: Summary of evidence (see Konstantinos Varvagiannis' reviews for details): 3 literature cases from 2 papers of patients with epileptic encephalopathy and GABRA5 missense variants: PMID:29961870, Butler et al. 2018 report a 2 year old boy with EIEE (seizure onset age 4 months) and a p.V294L variant in GABRA5. Cognitive and motor development slowed at the time of seizure onset. A de novo variant in MIA2 was also detected but was considered unlikely to contribute to the patients phenotypes due to allele frequencies in the gnomAD database. PMID:31056671, Hernandez et al. 2019 screened a cohort of patients with epilepsy and ID and report 2 individuals with EIEE and GABRA5 missense variants (V294F and S413F). Seizures included focal, febrile, focal and tonic, epileptic spasms and status epilepticus. Both had severe ID and delayed motor development.
19 Sep 2019	Early onset or syndromic epilepsy v1.335	GABRA1	Rebecca Foulger Publications for gene: GABRA1 were set to 24623842; 11992121; 21714819; 16718694
19 Sep 2019	Early onset or syndromic epilepsy v1.334	GABRA2	Rebecca Foulger commented on gene: GABRA2: Summary of evidence (see Konstantinos Varvagiannis' reviews for details): Sufficient cases in OMIM and the literature to associate GABRA2 with 'Epileptic encephalopathy, early infantile, 78, 618557'. PMID:29422393, Orenstein et al., 2018 report a male of unrelated Ashkenazi Jewish parents with EIEE-78 and poor cognitive development, and a de novo heterozygous variant in GABRA2 (N335H). Functional studies were not performed but the variant was absent in ExAC and gnomAD controls. PMID:29961870, Butler et al. 2018 report an 11 year old girls with EIEE-78 who had multiple seizures starting age 6 weeks, and a de novo heterozygous variant in GABRA2 (T292K). PMID:31032849, Maljevic et al., 2019 decribe 5 patients (3 sporadic cases and 2 siblings) with four novel de novo GABRA2 missense variants (Val284Ala, Leu291Val, Met263Thr, Phe325Leu). All patients had seizures (Table 1) with onset 1day - 17years. The siblings inherited the variant from a mosaic father. https://doi.org/10.1101/678219: Sanchis-Juan et al., 2019 identified a de novo missense variant in GABRA2 gene (Pro280Leu) in a 10 year old girl with EIEE and developmental delay.
19 Sep 2019	Early onset or syndromic epilepsy v1.334	GABRA2	Rebecca Foulger Phenotypes for gene: GABRA2 were changed from Epileptic encephalopathy, early infantile, 78 (MIM 618557) to Epileptic encephalopathy, early infantile, 78, 618557
19 Sep 2019	Early onset or syndromic epilepsy v1.333	KATNB1	Rebecca Foulger Phenotypes for gene: KATNB1 were changed from Lissencephaly 6, with microcephaly, 616212 to Lissencephaly 6, with microcephaly, 616212; seizures
19 Sep 2019	Early onset or syndromic epilepsy v1.332	KATNB1	Rebecca Foulger commented on gene: KATNB1
19 Sep 2019	Early onset or syndromic epilepsy v1.332	KATNB1	Rebecca Foulger Phenotypes for gene: KATNB1 were changed from Lissencephaly 6, with microcephaly (MIM 616212) to Lissencephaly 6, with microcephaly, 616212
17 Sep 2019	Early onset or syndromic epilepsy v1.331	GRIA2	Rebecca Foulger Source Wessex and West Midlands GLH was added to GRIA2.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	KMT5B	Rebecca Foulger Source Wessex and West Midlands GLH was added to KMT5B.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	KCNH5	Rebecca Foulger Source Wessex and West Midlands GLH was added to KCNH5.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	KCND2	Rebecca Foulger Source Wessex and West Midlands GLH was added to KCND2.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	CSNK2A1	Rebecca Foulger Source Wessex and West Midlands GLH was added to CSNK2A1.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	BCORL1	Rebecca Foulger Source Wessex and West Midlands GLH was added to BCORL1.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	ZNF142	Rebecca Foulger Source Wessex and West Midlands GLH was added to ZNF142.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	ZMIZ1	Rebecca Foulger Source Wessex and West Midlands GLH was added to ZMIZ1.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	USP7	Rebecca Foulger Source Wessex and West Midlands GLH was added to USP7.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	TRRAP	Rebecca Foulger Source Wessex and West Midlands GLH was added to TRRAP.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	TRPM3	Rebecca Foulger Source Wessex and West Midlands GLH was added to TRPM3.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	SLC35A3	Rebecca Foulger Source Wessex and West Midlands GLH was added to SLC35A3.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	RNF13	Rebecca Foulger Source Wessex and West Midlands GLH was added to RNF13.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	PAK1	Rebecca Foulger Source Wessex and West Midlands GLH was added to PAK1.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	NUS1	Rebecca Foulger Source Wessex and West Midlands GLH was added to NUS1.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	LSS	Rebecca Foulger Source Wessex and West Midlands GLH was added to LSS.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	FUK	Rebecca Foulger Source Wessex and West Midlands GLH was added to FUK.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	CLCN6	Rebecca Foulger Source Wessex and West Midlands GLH was added to CLCN6.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	AIMP2	Rebecca Foulger Source Wessex and West Midlands GLH was added to AIMP2.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	AFF3	Rebecca Foulger Source Wessex and West Midlands GLH was added to AFF3.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	ZDHHC9	Rebecca Foulger Source Wessex and West Midlands GLH was added to ZDHHC9.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	WARS2	Rebecca Foulger Source Wessex and West Midlands GLH was added to WARS2.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	VPS11	Rebecca Foulger Source Wessex and West Midlands GLH was added to VPS11.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	VAMP2	Rebecca Foulger Source Wessex and West Midlands GLH was added to VAMP2.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	SNAP25	Rebecca Foulger Source Wessex and West Midlands GLH was added to SNAP25.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	SMARCC2	Rebecca Foulger Source Wessex and West Midlands GLH was added to SMARCC2.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	PPP2CA	Rebecca Foulger Source Wessex and West Midlands GLH was added to PPP2CA.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	PIGB	Rebecca Foulger Source Wessex and West Midlands GLH was added to PIGB.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	PARS2	Rebecca Foulger Source Wessex and West Midlands GLH was added to PARS2.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	P4HTM	Rebecca Foulger Source Wessex and West Midlands GLH was added to P4HTM.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	NBEA	Rebecca Foulger Source Wessex and West Midlands GLH was added to NBEA.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	KMT2E	Rebecca Foulger Source Wessex and West Midlands GLH was added to KMT2E.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	KCNT2	Rebecca Foulger Source Wessex and West Midlands GLH was added to KCNT2.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	DHPS	Rebecca Foulger Source Wessex and West Midlands GLH was added to DHPS.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	DEGS1	Rebecca Foulger Source Wessex and West Midlands GLH was added to DEGS1.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	CTNNA2	Rebecca Foulger Source Wessex and West Midlands GLH was added to CTNNA2.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	CACNA1B	Rebecca Foulger Source Wessex and West Midlands GLH was added to CACNA1B.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	ATN1	Rebecca Foulger Source Wessex and West Midlands GLH was added to ATN1.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	AP2M1	Rebecca Foulger Source Wessex and West Midlands GLH was added to AP2M1.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	ALKBH8	Rebecca Foulger Source Wessex and West Midlands GLH was added to ALKBH8.
17 Sep 2019	Early onset or syndromic epilepsy v1.331	ACTL6B	Rebecca Foulger Source Wessex and West Midlands GLH was added to ACTL6B.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	GRIA2	Rebecca Foulger Source NHS GMS was added to GRIA2.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	KMT5B	Rebecca Foulger Source NHS GMS was added to KMT5B.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	KCNH5	Rebecca Foulger Source NHS GMS was added to KCNH5.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	KCND2	Rebecca Foulger Source NHS GMS was added to KCND2.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	CSNK2A1	Rebecca Foulger Source NHS GMS was added to CSNK2A1.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	BCORL1	Rebecca Foulger Source NHS GMS was added to BCORL1.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	ZNF142	Rebecca Foulger Source NHS GMS was added to ZNF142.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	ZMIZ1	Rebecca Foulger Source NHS GMS was added to ZMIZ1.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	USP7	Rebecca Foulger Source NHS GMS was added to USP7.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	TRRAP	Rebecca Foulger Source NHS GMS was added to TRRAP.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	TRPM3	Rebecca Foulger Source NHS GMS was added to TRPM3.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	SLC35A3	Rebecca Foulger Source NHS GMS was added to SLC35A3.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	RNF13	Rebecca Foulger Source NHS GMS was added to RNF13.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	PAK1	Rebecca Foulger Source NHS GMS was added to PAK1.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	NUS1	Rebecca Foulger Source NHS GMS was added to NUS1.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	LSS	Rebecca Foulger Source NHS GMS was added to LSS.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	FUK	Rebecca Foulger Source NHS GMS was added to FUK.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	CLCN6	Rebecca Foulger Source NHS GMS was added to CLCN6.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	AIMP2	Rebecca Foulger Source NHS GMS was added to AIMP2.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	AFF3	Rebecca Foulger Source NHS GMS was added to AFF3.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	ZDHHC9	Rebecca Foulger Source NHS GMS was added to ZDHHC9.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	WARS2	Rebecca Foulger Source NHS GMS was added to WARS2.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	VPS11	Rebecca Foulger Source NHS GMS was added to VPS11.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	VAMP2	Rebecca Foulger Source NHS GMS was added to VAMP2.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	SNAP25	Rebecca Foulger Source NHS GMS was added to SNAP25.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	SMARCC2	Rebecca Foulger Source NHS GMS was added to SMARCC2.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	PPP2CA	Rebecca Foulger Source NHS GMS was added to PPP2CA.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	PIGB	Rebecca Foulger Source NHS GMS was added to PIGB.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	PARS2	Rebecca Foulger Source NHS GMS was added to PARS2.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	P4HTM	Rebecca Foulger Source NHS GMS was added to P4HTM.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	NBEA	Rebecca Foulger Source NHS GMS was added to NBEA.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	KMT2E	Rebecca Foulger Source NHS GMS was added to KMT2E.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	KCNT2	Rebecca Foulger Source NHS GMS was added to KCNT2.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	DHPS	Rebecca Foulger Source NHS GMS was added to DHPS.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	DEGS1	Rebecca Foulger Source NHS GMS was added to DEGS1.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	CTNNA2	Rebecca Foulger Source NHS GMS was added to CTNNA2.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	CACNA1B	Rebecca Foulger Source NHS GMS was added to CACNA1B.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	ATN1	Rebecca Foulger Source NHS GMS was added to ATN1.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	AP2M1	Rebecca Foulger Source NHS GMS was added to AP2M1.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	ALKBH8	Rebecca Foulger Source NHS GMS was added to ALKBH8.
17 Sep 2019	Early onset or syndromic epilepsy v1.330	ACTL6B	Rebecca Foulger Source NHS GMS was added to ACTL6B.
15 Sep 2019	Early onset or syndromic epilepsy v1.329	CACNA2D2	Konstantinos Varvagiannis reviewed gene: CACNA2D2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23339110, 24358150, 30410802, 29997391, 31402629, 11487633, 11756448, 4177347, 14660671, 15331424; Phenotypes: Cerebellar atrophy with seizures and variable developmental delay (MIM 618501); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
10 Sep 2019	Early onset or syndromic epilepsy v1.329	PIGP	Rebecca Foulger changed review comment from: 2 independent cases reported in OMIM: 2 compound heterozygous siblings with early infantile epileptic encephalopathy-55 reported by Johnstone et al., 2017 (PMID:28334793). Plus a 2-year-old girl, with a homozygous 1bp deletion, born of unrelated parents, with EIEE55 reported by Krenn et al.,2019 (PMID:31139695).; to: Summary of cases (see Konstantinos Varvagiannis' review for details). 2 independent cases reported in OMIM: 2 compound heterozygous siblings with early infantile epileptic encephalopathy-55 reported by Johnstone et al., 2017 (PMID:28334793). Plus a 2-year-old girl, with a homozygous 1bp deletion, born of unrelated parents, with EIEE55 reported by Krenn et al.,2019 (PMID:31139695). The third case reported by Konstantinos comes from LOVD.
10 Sep 2019	Early onset or syndromic epilepsy v1.329	PIGP	Rebecca Foulger commented on gene: PIGP
10 Sep 2019	Early onset or syndromic epilepsy v1.329	PIGP	Rebecca Foulger Phenotypes for gene: PIGP were changed from Generalized hypotonia; Global developmental delay; Seizures; Intellectual disability; Feeding difficulties; Cortical visual impairment to ?Epileptic encephalopathy, early infantile, 55, 617599; Generalized hypotonia; Global developmental delay; Seizures; Intellectual disability; Feeding difficulties; Cortical visual impairment
10 Sep 2019	Early onset or syndromic epilepsy v1.328	GABRA5	Rebecca Foulger changed review comment from: Added missense tag because, as Konstantinos Varvagiannis notes, only missense variants reported to date for Epileptic Encephalopathy.; to: Added missense tag because, as Konstantinos Varvagiannis notes, only missense GABRA5 variants reported to date for Epileptic Encephalopathy.
10 Sep 2019	Early onset or syndromic epilepsy v1.328	GABRA5	Rebecca Foulger changed review comment from: Added missense tag because, as Konstantinos Varvagiannis notes, only missense variants reported to date.; to: Added missense tag because, as Konstantinos Varvagiannis notes, only missense variants reported to date for Epileptic Encephalopathy.
10 Sep 2019	Early onset or syndromic epilepsy v1.328	GABRA5	Rebecca Foulger commented on gene: GABRA5
10 Sep 2019	Early onset or syndromic epilepsy v1.328	GABRA5	Rebecca Foulger Phenotypes for gene: GABRA5 were changed from Epileptic encephalopathy, early infantile, 79 (MIM 618559) to Epileptic encephalopathy, early infantile, 79, 618559
10 Sep 2019	Early onset or syndromic epilepsy v1.327	GABRA5	Rebecca Foulger Publications for gene: GABRA5 were set to 29961870
10 Sep 2019	Early onset or syndromic epilepsy v1.326	GABRA5	Rebecca Foulger Tag missense tag was added to gene: GABRA5.
10 Sep 2019	Early onset or syndromic epilepsy v1.326	GABRA2	Rebecca Foulger Deleted their comment
10 Sep 2019	Early onset or syndromic epilepsy v1.326	GABRA2	Rebecca Foulger commented on gene: GABRA2: Added 'missense' tag based on Konstantinos Varvagiannis' comment that all variants to-date are missense variants.
10 Sep 2019	Early onset or syndromic epilepsy v1.326	GABRA2	Rebecca Foulger Tag missense tag was added to gene: GABRA2.
10 Sep 2019	Early onset or syndromic epilepsy v1.326	GABRA2	Rebecca Foulger commented on gene: GABRA2
10 Sep 2019	Early onset or syndromic epilepsy v1.326	HNRNPR	Catherine Snow Tag watchlist tag was added to gene: HNRNPR.
10 Sep 2019	Early onset or syndromic epilepsy v1.326	HNRNPR	Catherine Snow Classified gene: HNRNPR as Amber List (moderate evidence)
10 Sep 2019	Early onset or syndromic epilepsy v1.326	HNRNPR	Catherine Snow Gene: hnrnpr has been classified as Amber List (Moderate Evidence).
10 Sep 2019	Early onset or syndromic epilepsy v1.325	HNRNPR	Catherine Snow reviewed gene: HNRNPR: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
10 Sep 2019	Early onset or syndromic epilepsy v1.325	GABRA2	Konstantinos Varvagiannis changed review comment from: Heterozygous pathogenic GABRA2 variants cause Epileptic encephalopathy, early infantile, 78 (MIM 618557) [new OMIM entry]. At least 8 relevant individuals have been reported to date in the following studies: - Orenstein et al. (2018 - PMID: 29422393) - 1 individual - Butler et al. (2018 - PMID: 29961870) - 1 subject - Maljevic et al. (2019 - PMID: 31032849 - 3 unrelated children as well as 2 affected sibs - Sanchis-Juan et al. (2019 - bioRxiv / https://doi.org/10.1101/678219) - 1 further patient In all affected individuals the variants were missense and - in almost all cases - had occurred as de novo events. The 2 sibs reported by Maljevic however, had inherited a missense variant from their unaffected mosaic parent. Clinical descriptions for individuals from the 3 studies are provided in OMIM and also summarized in the suppl. table 1 by Sanchis-Juan et al. (https://www.biorxiv.org/content/biorxiv/early/2019/06/21/678219/DC2/embed/media-2.xlsx). Seizures, DD and ID (relevant to the current panel) are among the reported features. Functional studies have been performed for most of the variants and are summarized for each one in the OMIM entry for GABRG2 and the aforementioned table as well. The following variants have been reported (NM_000807.2): c.1003A>C - p.Asn335His (dn) / c.875C>A - Thr292Lys (dn) / c.871C>G - p.Leu291Val (dn) / c.788T>C - p.Met263Thr (dn) / c.851T>C - p.Val284Ala (dn) / c.975C>A - p.Phe325Leu (inherited from mosaic parent) / c.839C>T - p.Pro280Leu (dn - Sanchis-Juan et al). As commented by Jenkins and Escayg (2019 - PMID: 31032848 / both among the authors of the 1st report) as well as by Sanchis-Juan et al., both loss- and gain- of function effects explain the pathogenicity of the various mutations reported to date. [In gnomAD GABRA2 has a Z-score for missense variants of 3.13 as well as a pLI of 1]. ------ GABRA2 is not associated with any phenotype in G2P. This gene is not commonly included in gene panels for ID offered by diagnostic laboratories. ------ As a result, GABRA2 can be considered for inclusion in the epilepsy and ID panels probably as green (several relevant individuals, several reported variants with supporting functional studies for most, etc.). [Consider inclusion in other possibly relevant gene panels eg. for ASD which was feature in some patients at relevant age and/or among those evaluated].; to: Heterozygous pathogenic GABRA2 variants cause Epileptic encephalopathy, early infantile, 78 (MIM 618557) [new OMIM entry]. At least 8 relevant individuals have been reported to date in the following studies: - Orenstein et al. (2018 - PMID: 29422393) - 1 individual - Butler et al. (2018 - PMID: 29961870) - 1 subject - Maljevic et al. (2019 - PMID: 31032849 - 3 unrelated children as well as 2 affected sibs - Sanchis-Juan et al. (2019 - bioRxiv / https://doi.org/10.1101/678219) - 1 further patient In all affected individuals the variants were missense and - in almost all cases - had occurred as de novo events. The 2 sibs reported by Maljevic however, had inherited a missense variant from their unaffected mosaic parent. Clinical descriptions for individuals from the 3 studies are provided in OMIM and also summarized, Maljevic - Table 1 (7 patients) and/or in the suppl. table 1 by Sanchis-Juan et al. (8 patients) (https://www.biorxiv.org/content/biorxiv/early/2019/06/21/678219/DC2/embed/media-2.xlsx). Seizures, DD and ID (relevant to the current panel) are among the reported features. Functional studies have been performed for most of the variants and are summarized for each one in the OMIM entry for GABRG2 and the aforementioned table as well. The following variants have been reported (NM_000807.2): c.1003A>C - p.Asn335His (dn) / c.875C>A - Thr292Lys (dn) / c.871C>G - p.Leu291Val (dn) / c.788T>C - p.Met263Thr (dn) / c.851T>C - p.Val284Ala (dn) / c.975C>A - p.Phe325Leu (inherited from mosaic parent) / c.839C>T - p.Pro280Leu (dn - Sanchis-Juan et al). As commented by Jenkins and Escayg (2019 - PMID: 31032848 / both among the authors of the 1st report) as well as by Sanchis-Juan et al., both loss- and gain- of function effects explain the pathogenicity of the various mutations reported to date. [In gnomAD GABRA2 has a Z-score for missense variants of 3.13 as well as a pLI of 1]. ------ GABRA2 is not associated with any phenotype in G2P. This gene is not commonly included in gene panels for ID offered by diagnostic laboratories. ------ As a result, GABRA2 can be considered for inclusion in the epilepsy and ID panels probably as green (several relevant individuals, several reported variants with supporting functional studies for most, etc.). [Consider inclusion in other possibly relevant gene panels eg. for ASD which was feature in some patients at relevant age and/or among those evaluated].
09 Sep 2019	Early onset or syndromic epilepsy v1.325	TRAPPC6B	Rebecca Foulger Publications for gene: TRAPPC6B were set to 28626029; 28397838
09 Sep 2019	Early onset or syndromic epilepsy v1.324	TRAPPC6B	Rebecca Foulger commented on gene: TRAPPC6B: The Amber review by Konstantinos Varvagiannis (25 Aug 2019) agrees with the current Amber rating of TRAPPC6B: therefore no further curation required.
09 Sep 2019	Early onset or syndromic epilepsy v1.324	GRIA2	Rebecca Foulger Classified gene: GRIA2 as Amber List (moderate evidence)
09 Sep 2019	Early onset or syndromic epilepsy v1.324	GRIA2	Rebecca Foulger Added comment: Comment on list classification: Changed rating of GRIA2 from Grey to Amber based on Amber post-Webex review from Helen Lord. Currently insufficient evidence for a diagnostic rating.
09 Sep 2019	Early onset or syndromic epilepsy v1.324	GRIA2	Rebecca Foulger Gene: gria2 has been classified as Amber List (Moderate Evidence).
09 Sep 2019	Early onset or syndromic epilepsy v1.323	NUS1	Rebecca Foulger Mode of inheritance for gene: NUS1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
09 Sep 2019	Early onset or syndromic epilepsy v1.322	NUS1	Rebecca Foulger Classified gene: NUS1 as Green List (high evidence)
09 Sep 2019	Early onset or syndromic epilepsy v1.322	NUS1	Rebecca Foulger Gene: nus1 has been classified as Green List (High Evidence).
09 Sep 2019	Early onset or syndromic epilepsy v1.321	NUS1	Rebecca Foulger commented on gene: NUS1: Updated rating from Amber to Green based on Green post-Webex review from Helen Lord. Also updated MOI from 'monoallelic' to 'BOTH monoallelic and biallelic' based on Helen's review.
09 Sep 2019	Early onset or syndromic epilepsy v1.321	ZMIZ1	Rebecca Foulger commented on gene: ZMIZ1: Kept rating as Amber based on Amber post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.321	ZDHHC9	Rebecca Foulger commented on gene: ZDHHC9: Kept rating as Green based on Green post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.321	WARS2	Rebecca Foulger commented on gene: WARS2: Kept rating as Green based on Green post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.321	VPS11	Rebecca Foulger commented on gene: VPS11: Kept rating as Green based on Green post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.321	VAMP2	Rebecca Foulger commented on gene: VAMP2: Kept rating as Green based on Green post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.321	SNAP25	Rebecca Foulger commented on gene: SNAP25: Kept rating as Green based on Green post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.321	SMARCC2	Rebecca Foulger commented on gene: SMARCC2: Kept rating as Green based on Green post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.321	SMARCC2	Rebecca Foulger Phenotypes for gene: SMARCC2 were changed from Global developmental delay; Intellectual disability; neurodevelopmental delay and growth retardation; prominent speech impairment, hypotonia, feeding difficulties, behavioral abnormalities, and dysmorphic features to Coffin-Siris syndrome 8, 618362; Global developmental delay; Intellectual disability; neurodevelopmental delay and growth retardation; prominent speech impairment, hypotonia, feeding difficulties, behavioral abnormalities, and dysmorphic features
09 Sep 2019	Early onset or syndromic epilepsy v1.320	SLC35A3	Rebecca Foulger commented on gene: SLC35A3: Kept rating as Amber based on Amber post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.320	RNF13	Rebecca Foulger commented on gene: RNF13: Kept rating as Amber based on Amber post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.320	PPP2CA	Rebecca Foulger commented on gene: PPP2CA: Kept rating as Green based on Green post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.320	POLG	Rebecca Foulger commented on gene: POLG: Kept rating as Green based on Green post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.320	POLG	Rebecca Foulger changed review comment from: Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene was added to the Genetic epilepsy syndromes panel after the initial panel was reviewed by West Midlands, Oxford and Wessex GLH: this gene was therefore reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.; to: Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.
09 Sep 2019	Early onset or syndromic epilepsy v1.320	PIGB	Rebecca Foulger commented on gene: PIGB: Kept rating as Green based on Green post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.320	PARS2	Rebecca Foulger commented on gene: PARS2: Kept rating as Green based on Green post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.320	PAK1	Rebecca Foulger Publications for gene: PAK1 were set to 30290153
09 Sep 2019	Early onset or syndromic epilepsy v1.319	P4HTM	Rebecca Foulger Phenotypes for gene: P4HTM were changed from Hypotonia, hyperventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities, 618493; Abnormality of the eye; Seizures; Dysautonomia; Central hypotonia; Muscular hypotonia; Hypoventilation; Intellectual disability; Sleep apnea; Global developmental delay to Hypotonia, hyperventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities, 618493; Seizures; Intellectual disability; Global developmental delay
09 Sep 2019	Early onset or syndromic epilepsy v1.318	P4HTM	Rebecca Foulger Phenotypes for gene: P4HTM were changed from Abnormality of the eye; Seizures; Dysautonomia; Central hypotonia; Muscular hypotonia; Hypoventilation; Intellectual disability; Sleep apnea; Global developmental delay to Hypotonia, hyperventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities, 618493; Abnormality of the eye; Seizures; Dysautonomia; Central hypotonia; Muscular hypotonia; Hypoventilation; Intellectual disability; Sleep apnea; Global developmental delay
09 Sep 2019	Early onset or syndromic epilepsy v1.317	NUS1	Rebecca Foulger Phenotypes for gene: NUS1 were changed from #617082 - ?Congenital disorder of glycosylation, type 1aa; #617831 - Mental retardation, autosomal dominant 55, with seizures; Abnormality of extrapyramidal motor function to ?Congenital disorder of glycosylation, type 1aa, 617082; Mental retardation, autosomal dominant 55, with seizures, 617831; Abnormality of extrapyramidal motor function
09 Sep 2019	Early onset or syndromic epilepsy v1.316	NBEA	Rebecca Foulger commented on gene: NBEA: Kept rating as Green based on Green post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.316	LSS	Rebecca Foulger commented on gene: LSS: Kept rating as Amber based on Amber post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.316	KMT5B	Rebecca Foulger commented on gene: KMT5B: Kept rating as Red based on Red post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.316	KMT5B	Rebecca Foulger Publications for gene: KMT5B were set to 29276005
09 Sep 2019	Early onset or syndromic epilepsy v1.315	KMT2E	Rebecca Foulger commented on gene: KMT2E: Kept rating as Green based on Green post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.315	KCNT2	Rebecca Foulger commented on gene: KCNT2: Kept rating as Green based on Green post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.315	KCNH5	Rebecca Foulger commented on gene: KCNH5: Kept rating as Red based on Red post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.315	KCNH5	Rebecca Foulger Publications for gene: KCNH5 were set to 23647072
09 Sep 2019	Early onset or syndromic epilepsy v1.314	FUK	Rebecca Foulger commented on gene: FUK: Kept rating as Amber based on Amber post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.314	DHPS	Rebecca Foulger commented on gene: DHPS: Kept rating as Green based on Green post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.314	DEGS1	Rebecca Foulger commented on gene: DEGS1: Kept rating as Green based on Green post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.314	CTNNA2	Rebecca Foulger commented on gene: CTNNA2: Kept rating as Green based on Green post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.314	CACNA1B	Rebecca Foulger commented on gene: CACNA1B: Kept rating as Green based on Green post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.314	BCORL1	Rebecca Foulger commented on gene: BCORL1: Kept rating as Red based on Red post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.314	BCORL1	Rebecca Foulger Phenotypes for gene: BCORL1 were changed from Intellectual disability and seizures to Intellectual disability and seizures; Shukla-Vernon syndrome, 301029
09 Sep 2019	Early onset or syndromic epilepsy v1.313	BCORL1	Rebecca Foulger Publications for gene: BCORL1 were set to 30941876
09 Sep 2019	Early onset or syndromic epilepsy v1.312	ATN1	Rebecca Foulger commented on gene: ATN1: Kept rating as Green based on Green post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.312	ATN1	Rebecca Foulger Phenotypes for gene: ATN1 were changed from Congenital hypotonia, epilepsy, developmental delay, and digital anomalies, 618494; Global developmental delay; Intellectual disability; Seizures to Congenital hypotonia, epilepsy, developmental delay, and digital anomalies, 618494; Global developmental delay; Intellectual disability; Seizures; Generalized hypotonia
09 Sep 2019	Early onset or syndromic epilepsy v1.311	ATN1	Rebecca Foulger Phenotypes for gene: ATN1 were changed from Abnormality of the kidney; Seizures; Hypotonia; Cleft palate; Developmental Delay; Abnormality of the cardiovascular system; Epilepsy; Generalized hypotonia; Feeding difficulties; Intellectual disability; Global developmental delay; Digit Abnormalities to Congenital hypotonia, epilepsy, developmental delay, and digital anomalies, 618494; Global developmental delay; Intellectual disability; Seizures
09 Sep 2019	Early onset or syndromic epilepsy v1.310	AP2M1	Rebecca Foulger commented on gene: AP2M1: Kept rating as Green based on Green post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.310	AP2M1	Rebecca Foulger Mode of pathogenicity for gene: AP2M1 was changed from Other to Other
09 Sep 2019	Early onset or syndromic epilepsy v1.309	ALKBH8	Rebecca Foulger Phenotypes for gene: ALKBH8 were changed from Global developmental delay; Seizures; Intellectual Disability; Developmental Delay; Intellectual disability to Intellectual developmental disorder, autosomal recessive 71, 618504; Global developmental delay; Seizures; Intellectual Disability; Developmental Delay; Intellectual disability
09 Sep 2019	Early onset or syndromic epilepsy v1.308	ACTL6B	Rebecca Foulger commented on gene: ACTL6B: Kept rating as Green based on Green post-Webex review from Helen Lord.
09 Sep 2019	Early onset or syndromic epilepsy v1.308	ACTL6B	Rebecca Foulger Phenotypes for gene: ACTL6B were changed from Global developmental delay; Intellectual disability; Seizures; Spasticity; epileptic encephalopathy to Epileptic encephalopathy, early infantile, 76, 618468; Global developmental delay; Intellectual disability; Seizures; Spasticity; epileptic encephalopathy
09 Sep 2019	Early onset or syndromic epilepsy v1.307	USP7	Rebecca Foulger Marked gene: USP7 as ready
09 Sep 2019	Early onset or syndromic epilepsy v1.307	USP7	Rebecca Foulger Gene: usp7 has been classified as Amber List (Moderate Evidence).
09 Sep 2019	Early onset or syndromic epilepsy v1.307	USP7	Rebecca Foulger commented on gene: USP7: Kept rating as Amber based on two post-Webex Amber reviews from Helen Lord and Alison Callaway.
09 Sep 2019	Early onset or syndromic epilepsy v1.307	TRPM3	Rebecca Foulger Marked gene: TRPM3 as ready
09 Sep 2019	Early onset or syndromic epilepsy v1.307	TRPM3	Rebecca Foulger Gene: trpm3 has been classified as Amber List (Moderate Evidence).
09 Sep 2019	Early onset or syndromic epilepsy v1.307	TRPM3	Rebecca Foulger Publications for gene: TRPM3 were set to 31278393
09 Sep 2019	Early onset or syndromic epilepsy v1.306	TRPM3	Rebecca Foulger commented on gene: TRPM3: Kept rating as Amber based on two post-Webex Amber reviews from Helen Lord and Alison Callaway.
09 Sep 2019	Early onset or syndromic epilepsy v1.306	KCND2	Rebecca Foulger commented on gene: KCND2: Kept rating as Red based on two post-Webex Red reviews from Helen Lord and Alison Callaway.
09 Sep 2019	Early onset or syndromic epilepsy v1.306	KCND2	Rebecca Foulger Publications for gene: KCND2 were set to 24501278; 16934482
09 Sep 2019	Early onset or syndromic epilepsy v1.305	KCND2	Rebecca Foulger Publications for gene: KCND2 were set to 24501278
09 Sep 2019	Early onset or syndromic epilepsy v1.304	CSNK2A1	Rebecca Foulger commented on gene: CSNK2A1: Kept rating as Red based on post-Webex reviews from Helen Lord and Alison Callaway: Although there is an argument to upgrade to Amber, epilepsy is not a major part of the overall phenotype so on balance kept rating as Red.
09 Sep 2019	Early onset or syndromic epilepsy v1.304	CSNK2A1	Rebecca Foulger Phenotypes for gene: CSNK2A1 were changed from seizures; Okur-Chung neurodevelopmental syndrome, 617062; CSNK2A1 syndrome to Neurodevelopmental abnormalities and dysmorphic features; seizures; Okur-Chung neurodevelopmental syndrome, 617062; CSNK2A1 syndrome
09 Sep 2019	Early onset or syndromic epilepsy v1.303	CSNK2A1	Rebecca Foulger Publications for gene: CSNK2A1 were set to 30655572
09 Sep 2019	Early onset or syndromic epilepsy v1.302	CLCN6	Rebecca Foulger Classified gene: CLCN6 as Red List (low evidence)
09 Sep 2019	Early onset or syndromic epilepsy v1.302	CLCN6	Rebecca Foulger Added comment: Comment on list classification: Changed rating from Amber to Red based on post-Webex reviews from Helen Lord and Alison Callaway: the current published association between CLCN6 and seizures is weak.
09 Sep 2019	Early onset or syndromic epilepsy v1.302	CLCN6	Rebecca Foulger Gene: clcn6 has been classified as Red List (Low Evidence).
09 Sep 2019	Early onset or syndromic epilepsy v1.301	AIMP2	Rebecca Foulger commented on gene: AIMP2: Kept rating as Amber based on post-Webex reviews from Helen Lord and Alison Callaway. Added 'watchlist' tag based on PMID:26795593 who report an additional case but there is uncertainty over the clinical significance of the reported variant.
09 Sep 2019	Early onset or syndromic epilepsy v1.301	AIMP2	Rebecca Foulger Tag watchlist tag was added to gene: AIMP2.
09 Sep 2019	Early onset or syndromic epilepsy v1.301	AIMP2	Rebecca Foulger Phenotypes for gene: AIMP2 were changed from Leukodystrophy, hypomyelinating, 17, 618006; neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis to Epileptic Encephalopathy; Infantile Spasms; Leukodystrophy, hypomyelinating, 17, 618006; neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis
09 Sep 2019	Early onset or syndromic epilepsy v1.300	AIMP2	Rebecca Foulger Publications for gene: AIMP2 were set to 29215095
08 Sep 2019	Early onset or syndromic epilepsy v1.299	GABRA2	Konstantinos Varvagiannis reviewed gene: GABRA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29422393, 29961870, 31032849, 31032848, doi.org/10.1101/678219; Phenotypes: Epileptic encephalopathy, early infantile, 78 (MIM 618557); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
08 Sep 2019	Early onset or syndromic epilepsy v1.299	GABRA2	Konstantinos Varvagiannis Deleted their review
08 Sep 2019	Early onset or syndromic epilepsy v1.299	GABRA2	Konstantinos Varvagiannis gene: GABRA2 was added gene: GABRA2 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: GABRA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: GABRA2 were set to 29422393; 29961870; 31032849; 31032848; doi.org/10.1101/678219 Phenotypes for gene: GABRA2 were set to Epileptic encephalopathy, early infantile, 78 (MIM 618557) Penetrance for gene: GABRA2 were set to unknown Review for gene: GABRA2 was set to GREEN Added comment: Heterozygous pathogenic GABRA2 variants cause Epileptic encephalopathy, early infantile, 78 (MIM 618557) [new OMIM entry]. At least 8 relevant individuals have been reported to date in the following studies: - Orenstein et al. (2018 - PMID: 29422393) - 1 individual - Butler et al. (2018 - PMID: 29961870) - 1 subject - Maljevic et al. (2019 - PMID: 31032849 - 3 unrelated children as well as 2 affected sibs - Sanchis-Juan et al. (2019 - bioRxiv / https://doi.org/10.1101/678219) - 1 further patient In almost all affected individuals, the variants were missense and had occurred as de novo events. The 2 sibs reported by Maljevic however, had inherited a missense variant from their unaffected mosaic parent. Clinical descriptions for individuals from the 3 studies are provided in OMIM and also summarized in the suppl. table 1 by Sanchis-Juan et al. (https://www.biorxiv.org/content/biorxiv/early/2019/06/21/678219/DC2/embed/media-2.xlsx?download=true). Seizures, DD and ID (relevant to the current panel) are among the reported features. Functional studies have been performed for most of the variants and are summarized for each one in the OMIM entry for GABRG2 and the aforementionned table as well. The following variants have been reported (NM_000807.2): c.1003A>C - p.Asn335His (dn) / c.875C>A - Thr292Lys (dn) / c.871C>G - p.Leu291Val (dn) / c.788T>C - p.Met263Thr (dn) / c.851T>C - p.Val284Ala (dn) / c.975C>A - p.Phe325Leu (inherited from mosaic parent) / c.839C>T - p.Pro280Leu (dn - Sanchis-Juan et al). As commented by Jenkins and Escayg (2019 - PMID: 31032848 / both among the authors of the 1st report) as well as by Sanchis-Juan et al., both loss- and gain- of function effects explain the pathogenicity of the various reported mutations to date. [In gnomAD GABRA2 has a Z-score for missense variants of 3.13 as well as a pLI of 1]. ------ GABRA2 is not associated with any phenotype in G2P. This gene is not commonly included in gene panels for ID offered by diagnostic laboratories. ------ As a result, GABRA2 can be considered for inclusion in the epilepsy and ID panels probably as green (several relevant individuals, several reported variants with supporting functional studies for most, etc.). [Consider inclusion in other possibly relevant gene panels eg. for ASD which was feature in some patients at relevant age and/or among those evaluated]. Sources: Literature
08 Sep 2019	Early onset or syndromic epilepsy v1.299	GABRA5	Konstantinos Varvagiannis reviewed gene: GABRA5: Rating: GREEN; Mode of pathogenicity: None; Publications: 29961870, 31056671; Phenotypes: Epileptic encephalopathy, early infantile, 79 (MIM 618559); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
08 Sep 2019	Early onset or syndromic epilepsy v1.299	GABRA5	Konstantinos Varvagiannis Deleted their review
08 Sep 2019	Early onset or syndromic epilepsy v1.299	GABRA5	Konstantinos Varvagiannis gene: GABRA5 was added gene: GABRA5 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: GABRA5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: GABRA5 were set to 29961870 Phenotypes for gene: GABRA5 were set to Epileptic encephalopathy, early infantile, 79 (MIM 618559) Penetrance for gene: GABRA5 were set to unknown Review for gene: GABRA5 was set to GREEN Added comment: Heterozygous pathogenic GABRA5 variants cause Epileptic encephalopathy, early infantile, 79 (MIM 618559) [entry recently updated in OMIM]. At least 3 relevant individuals with this diagnosis have been reported to date: - Butler et al. (2018 - PMID: 29961870) described a 2 y.o. boy with early infantile epileptic encephalopathy (seizure onset at the age of 4m). The boy was found to harbor a de novo missense variant (NM_000810.3:c.880G>C - p.Val294Leu) identified following trio-WGS and confirmed by Sanger sequencing. Studies in HEK293 cells demonstrated expression at the surface and incorporation of the mutant subunit in the channel. The α5(V294L)β2γ2s receptors were 10 times more sensitive to GABA compared to wt, but were more likely to desensitize leading to reduced maximum GABA-evoked currents. - Hernandez et al. (2019 - PMID: 31056671) reported on 2 unrelated individuals with early-onset epileptic encephalopathy due to de novo GABRA5 variants identified by targeted NGS sequencing (480 epilepsy-related genes): A 3y 10m male with seizure onset at the age of 4m, severe motor delay and ID, frontotemporal atrophy and thin CC upon MRI imaging was found to harbor a de novo missense variant (NM_000810.3:c.880G>T / p.Val294Phe). A further unrelated subject (a 7 y.o. male) with seizure onset at the age of 3 months, severe DD and ID and cortical atrophy / thin CC upon MRI imaging was heterozygous for another missense variant which had occurred as a de novo event (NM_000810.3:c.1238C>T - p.Ser413Phe). Functional studies: Expression of HA-tagged α5(V294F) subunits at dendritic GABAergic synapses of rat hippocampal neurons was decreased compared to wt, in contrast with the expression of α5(S413F) subunits which was similar to wt. As the α5(V294F) appeared accumulated in the soma of the neurons, the authors performed additional studies – using HEK293T cells – to show that while the α5(S413F) spread outside the ER, α5(V294F) subunits localized to the ER. This was suggestive of a trafficking defect/ER retention. Co-expression of wt or mutant HA-tagged subunits, with β3 and γ2 subunits in HEK293T cells was carried out to assess assembly and trafficking to cell membranes. Reduced surface levels as well as total (whole cell lysate) levels were shown for α5(V294F). Surface levels and total levels of the α5(S413F) were not changed compared to wt. Surface levels of the β3 subunit were however lower in the case of α5(S413F), a finding which could be suggestive of a dominant negative effect. Both GABRA5 mutations resulted in decreased GABA-evoked current amplitudes in both neuronal and non-neuronal (HEK293T) cells. ------- The corresponding phenotype in OMIM is Epileptic encephalopathy, early infantile, 79 (618559). GABRA5 is not associated with any phenotype in G2P. This gene is included in gene panels for ID offered by some diagnostic laboratories (eg. GeneDx). ------- As a result, GABRA5 can be considered for inclusion in the ID and epilepsy panels probably as green (relevant phenotype, 3 unrelated individuals, 3 variants, supporting functional studies for all variants) or amber. Sources: Literature
07 Sep 2019	Early onset or syndromic epilepsy v1.299	SLC35A2	Rebecca Foulger Marked gene: SLC35A2 as ready
07 Sep 2019	Early onset or syndromic epilepsy v1.299	SLC35A2	Rebecca Foulger Gene: slc35a2 has been classified as Green List (High Evidence).
07 Sep 2019	Early onset or syndromic epilepsy v1.299	SLC35A2	Rebecca Foulger Added comment: Comment on mode of inheritance: Kept Mode of Inheritance as XLD based on post-Webex review by Helen Lord.
07 Sep 2019	Early onset or syndromic epilepsy v1.299	SLC35A2	Rebecca Foulger Mode of inheritance for gene: SLC35A2 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
07 Sep 2019	Early onset or syndromic epilepsy v1.298	SLC35A2	Rebecca Foulger Publications for gene: SLC35A2 were set to 24115232; 27743886; 30746764; 30584598; 29679388
07 Sep 2019	Early onset or syndromic epilepsy v1.297	SLC1A2	Rebecca Foulger Marked gene: SLC1A2 as ready
07 Sep 2019	Early onset or syndromic epilepsy v1.297	SLC1A2	Rebecca Foulger Gene: slc1a2 has been classified as Green List (High Evidence).
07 Sep 2019	Early onset or syndromic epilepsy v1.297	SLC1A2	Rebecca Foulger Added comment: Comment on mode of inheritance: Kept Mode of Inheritance as 'BOTH monoallelic and biallelic' based on post-Webex review by Helen Lord.
07 Sep 2019	Early onset or syndromic epilepsy v1.297	SLC1A2	Rebecca Foulger Mode of inheritance for gene: SLC1A2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
07 Sep 2019	Early onset or syndromic epilepsy v1.296	SLC16A2	Rebecca Foulger Marked gene: SLC16A2 as ready
07 Sep 2019	Early onset or syndromic epilepsy v1.296	SLC16A2	Rebecca Foulger Gene: slc16a2 has been classified as Green List (High Evidence).
07 Sep 2019	Early onset or syndromic epilepsy v1.296	SLC16A2	Rebecca Foulger Added comment: Comment on mode of inheritance: Updated Mode of Inheritance from XLR to XLD based on post-Webex review by Helen Lord.
07 Sep 2019	Early onset or syndromic epilepsy v1.296	SLC16A2	Rebecca Foulger Mode of inheritance for gene: SLC16A2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
07 Sep 2019	Early onset or syndromic epilepsy v1.295	SLC16A2	Rebecca Foulger Phenotypes for gene: SLC16A2 were changed from Allan-Herndon-Dudley syndrome, 300523 to Allan-Herndon-Dudley syndrome, 300523; AHDS
07 Sep 2019	Early onset or syndromic epilepsy v1.294	SLC16A2	Rebecca Foulger Publications for gene: SLC16A2 were set to 27212794; 15980113
07 Sep 2019	Early onset or syndromic epilepsy v1.293	SLC16A2	Rebecca Foulger Phenotypes for gene: SLC16A2 were changed from Allan-Herndon-Dudley syndrome to Allan-Herndon-Dudley syndrome, 300523
07 Sep 2019	Early onset or syndromic epilepsy v1.292	SLC16A2	Rebecca Foulger Publications for gene: SLC16A2 were set to Maranduba et al (2006) J Med Genet 43: 457_460
07 Sep 2019	Early onset or syndromic epilepsy v1.291	SLC12A5	Rebecca Foulger Marked gene: SLC12A5 as ready
07 Sep 2019	Early onset or syndromic epilepsy v1.291	SLC12A5	Rebecca Foulger Gene: slc12a5 has been classified as Green List (High Evidence).
07 Sep 2019	Early onset or syndromic epilepsy v1.291	SLC12A5	Rebecca Foulger Phenotypes for gene: SLC12A5 were changed from epilepsy of infancy with migrating focal seizures (EIMFS) to epilepsy of infancy with migrating focal seizures (EIMFS); Epileptic encephalopathy, early infantile, 34, 616645; {Epilepsy, idiopathic generalized, susceptibility to, 14}, 616685
07 Sep 2019	Early onset or syndromic epilepsy v1.290	SLC12A5	Rebecca Foulger Publications for gene: SLC12A5 were set to PMID: 26333769; 24668262
07 Sep 2019	Early onset or syndromic epilepsy v1.289	SLC12A5	Rebecca Foulger Mode of inheritance for gene: SLC12A5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
07 Sep 2019	Early onset or syndromic epilepsy v1.288	SLC12A5	Rebecca Foulger Added comment: Comment on mode of inheritance: Changed Mode of Inheritance from 'BOTH monoallelic and bialleic, autosomal or pseudoautosomal' to 'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal' based on post-Webex review by Helen Lord.
07 Sep 2019	Early onset or syndromic epilepsy v1.288	SLC12A5	Rebecca Foulger Mode of inheritance for gene: SLC12A5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
07 Sep 2019	Early onset or syndromic epilepsy v1.287	PIGA	Rebecca Foulger Marked gene: PIGA as ready
07 Sep 2019	Early onset or syndromic epilepsy v1.287	PIGA	Rebecca Foulger Gene: piga has been classified as Green List (High Evidence).
07 Sep 2019	Early onset or syndromic epilepsy v1.287	PIGA	Rebecca Foulger Added comment: Comment on mode of inheritance: Kept Mode of Inheritance as XLR based on post-Webex review by Helen Lord.
07 Sep 2019	Early onset or syndromic epilepsy v1.287	PIGA	Rebecca Foulger Mode of inheritance for gene: PIGA was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
07 Sep 2019	Early onset or syndromic epilepsy v1.286	PIGA	Rebecca Foulger Phenotypes for gene: PIGA were changed from Multiple congenital anomalies-hypotonia-seizures syndrome 2 to Multiple congenital anomalies-hypotonia-seizures syndrome 2, 300868
07 Sep 2019	Early onset or syndromic epilepsy v1.285	PIGA	Rebecca Foulger Publications for gene: PIGA were set to Johnston et al (2012) Am J Hum Genet 90, 295 300
07 Sep 2019	Early onset or syndromic epilepsy v1.284	NRXN1	Rebecca Foulger Marked gene: NRXN1 as ready
07 Sep 2019	Early onset or syndromic epilepsy v1.284	NRXN1	Rebecca Foulger Gene: nrxn1 has been classified as Green List (High Evidence).
07 Sep 2019	Early onset or syndromic epilepsy v1.284	NRXN1	Rebecca Foulger changed review comment from: Comment on mode of inheritance: Kept Mode of Inheritance as 'BOTH monoallelic and biallelic' based on Post-Webex review by Helen Lord.; to: Comment on mode of inheritance: Kept Mode of Inheritance as 'BOTH monoallelic and biallelic' based on post-Webex review by Helen Lord.
07 Sep 2019	Early onset or syndromic epilepsy v1.284	NRXN1	Rebecca Foulger Publications for gene: NRXN1 were set to 21964664; 19896112; 30031152; 23533028
07 Sep 2019	Early onset or syndromic epilepsy v1.283	NRXN1	Rebecca Foulger Added comment: Comment on mode of inheritance: Kept Mode of Inheritance as 'BOTH monoallelic and biallelic' based on Post-Webex review by Helen Lord.
07 Sep 2019	Early onset or syndromic epilepsy v1.283	NRXN1	Rebecca Foulger Mode of inheritance for gene: NRXN1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
07 Sep 2019	Early onset or syndromic epilepsy v1.282	MED12	Rebecca Foulger Marked gene: MED12 as ready
07 Sep 2019	Early onset or syndromic epilepsy v1.282	MED12	Rebecca Foulger Gene: med12 has been classified as Green List (High Evidence).
07 Sep 2019	Early onset or syndromic epilepsy v1.282	MED12	Rebecca Foulger Added comment: Comment on mode of inheritance: Updated Mode of Inheritance from XLR to XLD based on Post-Webex review by Helen Lord.
07 Sep 2019	Early onset or syndromic epilepsy v1.282	MED12	Rebecca Foulger Mode of inheritance for gene: MED12 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
07 Sep 2019	Early onset or syndromic epilepsy v1.281	MAGI2	Rebecca Foulger Added comment: Comment on mode of inheritance: Updated Mode of Inheritance from 'BOTH monoallelic and biallelic' to 'BIALLELIC' based on Post-Webex review by Helen Lord (AD inheritance was based on deletions including the MAGI2 gene).
07 Sep 2019	Early onset or syndromic epilepsy v1.281	MAGI2	Rebecca Foulger Mode of inheritance for gene: MAGI2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
07 Sep 2019	Early onset or syndromic epilepsy v1.280	MAGI2	Rebecca Foulger changed review comment from: Comment on mode of inheritance: OMIM lists AR inheritance for 'Nephrotic syndrome, type 15' (MIM:617609). Gene2Phenotype lists 'monoallelic' inheritance for EARLY ONSET EPILEPTIC ENCEPHALOPATHY.; to: Comment on mode of inheritance: OMIM lists AR inheritance for 'Nephrotic syndrome, type 15' (MIM:617609). Gene2Phenotype lists 'monoallelic' inheritance for EARLY ONSET EPILEPTIC ENCEPHALOPATHY based on PMID:18565486 which examines deletions spanning MAGI2.
07 Sep 2019	Early onset or syndromic epilepsy v1.280	IKBKG	Rebecca Foulger Marked gene: IKBKG as ready
07 Sep 2019	Early onset or syndromic epilepsy v1.280	IKBKG	Rebecca Foulger Gene: ikbkg has been classified as Green List (High Evidence).
07 Sep 2019	Early onset or syndromic epilepsy v1.280	IKBKG	Rebecca Foulger Publications for gene: IKBKG were set to 30151858; 28794079; 24339369
07 Sep 2019	Early onset or syndromic epilepsy v1.279	IKBKG	Rebecca Foulger Added comment: Comment on mode of inheritance: Kept Mode of Inheritance as XLD based on Post-Webex review by Helen Lord.
07 Sep 2019	Early onset or syndromic epilepsy v1.279	IKBKG	Rebecca Foulger Mode of inheritance for gene: IKBKG was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
07 Sep 2019	Early onset or syndromic epilepsy v1.278	IDH2	Rebecca Foulger Marked gene: IDH2 as ready
07 Sep 2019	Early onset or syndromic epilepsy v1.278	IDH2	Rebecca Foulger Gene: idh2 has been classified as Green List (High Evidence).
07 Sep 2019	Early onset or syndromic epilepsy v1.278	IDH2	Rebecca Foulger Added comment: Comment on mode of inheritance: Kept Mode of Inheritance as MONOALLELIC based on post-Webex review from Helen Lord. Note that the rating of IDH2 was not discussed on the group Webex (2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy) because IDH2 has a Green rating on the 'Inborn errors of metabolism' panel, and therefore will be Green on the Epilepsy super panel for R59.
07 Sep 2019	Early onset or syndromic epilepsy v1.278	IDH2	Rebecca Foulger Mode of inheritance for gene: IDH2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
07 Sep 2019	Early onset or syndromic epilepsy v1.277	HEPACAM	Rebecca Foulger Marked gene: HEPACAM as ready
07 Sep 2019	Early onset or syndromic epilepsy v1.277	HEPACAM	Rebecca Foulger Gene: hepacam has been classified as Green List (High Evidence).
07 Sep 2019	Early onset or syndromic epilepsy v1.277	HEPACAM	Rebecca Foulger Added comment: Comment on mode of inheritance: Kept Mode of Inheritance as BIALLELIC based on post-Webex review from Helen Lord, and original comment from Zornitza Stark that AD form is not associated with seizures.
07 Sep 2019	Early onset or syndromic epilepsy v1.277	HEPACAM	Rebecca Foulger Mode of inheritance for gene: HEPACAM was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
07 Sep 2019	Early onset or syndromic epilepsy v1.276	DEAF1	Rebecca Foulger Marked gene: DEAF1 as ready
07 Sep 2019	Early onset or syndromic epilepsy v1.276	DEAF1	Rebecca Foulger Gene: deaf1 has been classified as Green List (High Evidence).
07 Sep 2019	Early onset or syndromic epilepsy v1.276	DEAF1	Rebecca Foulger Phenotypes for gene: DEAF1 were changed from ?Dyskinesia, seizures, and intellectual developmental disorder 617171 to ?Dyskinesia, seizures, and intellectual developmental disorder, 617171
07 Sep 2019	Early onset or syndromic epilepsy v1.275	DEAF1	Rebecca Foulger Added comment: Comment on mode of inheritance: Changed Mode of Inheritance from 'BOTH monoallelic and biallelic' to 'BIALLELIC' based on post-Webex reviews from Helen Lord. The original comment from West Midlands, Oxford and Wessex GLH (uploaded for Tracy Lester) also supports biallelic inheritance.
07 Sep 2019	Early onset or syndromic epilepsy v1.275	DEAF1	Rebecca Foulger Mode of inheritance for gene: DEAF1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
07 Sep 2019	Early onset or syndromic epilepsy v1.274	PIGP	Konstantinos Varvagiannis changed review comment from: Johnstone et al. (2017 - PMID: 28334793) report on 2 sibs born to non-consanguineous parents of French-Irish ancestry. Both presented with seizures (onset at the age of 2 and 7 weeks respectively), hypotonia and profound DD. Other features included CVI and feeding difficulties. Extensive metabolic testing as well as prior genetic testing (ARX, STXBP1, MECP2, aCGH) in the family were non-diagnostic. WES suggested the presence of 2 PIGP variants with Sanger sequencing used for confirmation and segregation studies. PIGP encodes a subunit of the enzyme that catalyzes the first step of glycophosphatidylinositol (GPI) anchor biosynthesis. Mutations in other genes whose proteins are in complex with PIGP (PIGA, PIGC, PIGQ, PIGY, DPM2) lead to similar phenotypes. The phenotype overall was also overlapping with the inherited GPI deficiencies (belonging to the broader group of CDGs). PIGP has 2 isoforms, which differ by 24 amino acids due to utilization of alternative start codons [corresponding to NM_153681.2 (158 aa) and NM_153682.2 (134 aa)]. The variants identified affected both transcripts with the first SNV leading either to loss of the start codon (NM_153682.2:c.2T>C - p.Met1Thr) or to substitution of a methionine at position 25(NM_153681.2:c.74T>C;p.Met25Thr). The second variant led to frameshift in the last exon of both transcripts predicting a longer protein product (NM_153681.2:c.456delA / p.Glu153AsnfsTer34 or NM_153682.2:c.384delA / p.Glu129AsnfsTer34). Overall extensive studies demonstrated decreased levels of PIGP mRNA in patient fibroblast, decreased amounts of mutant protein in tranfected HEK293 cells. The decreased levels of GPI-APs further supported the effect of variants : - mRNA levels in patient fibroblasts were reduced compared to controls. Conclusions could not be drawn from Western blot, since no antibodies could specifically detect PIGP. HEK293 cells transfected of mt or wt HA-tagged PIGP cDNA led to undetectable amounts for the first variant (both M1T/M25T) and a protein product of increased molecular weight for the frameshift one. - Flow cytometry of patient granulocytes indicated reduced signal of CD16 (a GPI-anchored protein) and FLAER (binding directly to the GPI anchor). - Reduced levels of GPI-APs were also observed in PIGP deficient HAP1 cells transfected with either wt, or mutant PIGP cDNA (of both isoforms for the M1T/M25T or isoform 2 for the frameshift mutation). -------- Krenn et al. (2019 - PMID: 31139695) described a patient born to non-consanguineous Polish parents. Features were highly similar to those reported by Johnstone et al. and incl. intractable infantile seizures (onset at 7m), hypotonia, severe DD and feeding difficulties. Metabolic work-up failed to identify an alternative diagnosis. WES revealed homozygosity for the frameshift variant reported by Johnstone et al. Sanger sequencing confirmed the variant and carrier state in both parents. Identified ROH of less than 7 Mb in the WES data, suggested a founder mutation rather than unreported consanguinity. The variant is present 9 times in gnomAD (AF of 3.2e-5 / no homozygotes). Flow cytometry of patient granulocytes, revealed markedly reduced expression of GPI-APs (CD157, CD59, FLAER) compared to parents/controls. ALP was normal in all aforementioned individuals (probably in line with PIGP being involved in the 1st step of the GPI anchor biosynthesis). -------- A further individual with phenotype of EIEE-55;GPIBD-14 is reported in LOVD [Individual #00246132]. This individual, born to conanguineous parents, was tested by WES and found to be homozygous for a frameshift variant, also affecting the last exon in both transcripts (NM_153681.2:c.384delA (p.Glu129ArgfsTer7) / NM_153682.2:c.312delA (p.Glu105ArgfsTer7). This was probably in agreement with segregation studies according to the respective entry. The specific variant is reported as pathogenic [variant ID #0000500090]. -------- ?Epileptic encephalopathy, early infantile, 55 (MIM 617599) is the corresponding phenotype in OMIM. There is no relevant G2P entry. PIGP is included in gene panels for ID offered by some diagnostic laboratories (eg. GeneDx). -------- As a result, PIGP can be considered for inclusion in the ID/epilepsy panels probably as green (3 individuals, role of the gene and similarity to other inherited GPI deficiencies, extensive supporting studies) or amber. (Please consider inclusion in other possibly relevant panels eg. CDGs, etc). Sources: Literature; to: Johnstone et al. (2017 - PMID: 28334793) report on 2 sibs born to non-consanguineous parents of French-Irish ancestry. Both presented with seizures (onset at the age of 2 and 7 weeks respectively), hypotonia and profound DD. Other features included CVI and feeding difficulties. Extensive metabolic testing as well as prior genetic testing (ARX, STXBP1, MECP2, aCGH) in the family were non-diagnostic. WES suggested the presence of 2 PIGP variants with Sanger sequencing used for confirmation and segregation studies. PIGP encodes a subunit of the enzyme that catalyzes the first step of glycophosphatidylinositol (GPI) anchor biosynthesis. Mutations in other genes whose proteins are in complex with PIGP (PIGA, PIGC, PIGQ, PIGY, DPM2) lead to similar phenotypes. The phenotype overall was also overlapping with the inherited GPI deficiencies (belonging to the broader group of CDGs). PIGP has 2 isoforms, which differ by 24 amino acids due to utilization of alternative start codons [corresponding to NM_153681.2 (158 aa) and NM_153682.2 (134 aa)]. The variants identified affected both transcripts with the first SNV leading either to loss of the start codon (NM_153682.2:c.2T>C - p.Met1Thr) or to substitution of a methionine at position 25(NM_153681.2:c.74T>C;p.Met25Thr). The second variant led to frameshift in the last exon of both transcripts predicting a longer protein product (NM_153681.2:c.456delA / p.Glu153AsnfsTer34 or NM_153682.2:c.384delA / p.Glu129AsnfsTer34). Overall extensive studies demonstrated decreased levels of PIGP mRNA in patient fibroblast, decreased amounts of mutant protein in tranfected HEK293 cells. The decreased levels of GPI-APs further supported the effect of variants : - mRNA levels in patient fibroblasts were reduced compared to controls. Conclusions could not be drawn from Western blot, since no antibodies could specifically detect PIGP. HEK293 cells transfected of mt or wt HA-tagged PIGP cDNA led to undetectable amounts for the first variant (both M1T/M25T) and a protein product of increased molecular weight for the frameshift one. - Flow cytometry of patient granulocytes indicated reduced signal of CD16 (a GPI-anchored protein) and FLAER (binding directly to the GPI anchor). - Reduced levels of GPI-APs were also observed in PIGP deficient HAP1 cells transfected with either wt, or mutant PIGP cDNA (of both isoforms for the M1T/M25T or isoform 2 for the frameshift mutation). -------- Krenn et al. (2019 - PMID: 31139695) described a patient born to non-consanguineous Polish parents. Features were highly similar to those reported by Johnstone et al. and incl. intractable infantile seizures (onset at 7m), hypotonia, severe DD and feeding difficulties. Metabolic work-up failed to identify an alternative diagnosis. WES revealed homozygosity for the frameshift variant reported by Johnstone et al. Sanger sequencing confirmed the variant and carrier state in both parents. Identified ROH of less than 7 Mb in the WES data, suggested a founder mutation rather than unreported consanguinity. The variant is present 9 times in gnomAD (AF of 3.2e-5 / no homozygotes). Flow cytometry of patient granulocytes, revealed markedly reduced expression of GPI-APs (CD157, CD59, FLAER) compared to parents/controls. ALP was normal in all aforementioned individuals (probably in line with PIGP being involved in the 1st step of the GPI anchor biosynthesis). -------- A further individual with phenotype of EIEE-55;GPIBD-14 is reported in LOVD [Individual #00246132]. This individual, born to consanguineous parents, was tested by WES and found to be homozygous for a frameshift variant, also affecting the last exon in both transcripts [NM_153681.2:c.384delA (p.Glu129ArgfsTer7) / NM_153682.2:c.312delA (p.Glu105ArgfsTer7)]. This was probably in agreement with segregation studies according to the respective entry. The specific variant is reported as pathogenic [variant ID #0000500090]. -------- ?Epileptic encephalopathy, early infantile, 55 (MIM 617599) is the corresponding phenotype in OMIM. There is no relevant G2P entry. PIGP is included in gene panels for ID offered by some diagnostic laboratories (eg. GeneDx). -------- As a result, PIGP can be considered for inclusion in the ID/epilepsy panels probably as green (3 individuals, role of the gene and similarity to other inherited GPI deficiencies, extensive supporting studies) or amber. (Please consider inclusion in other possibly relevant panels eg. CDGs, etc). Sources: Literature
07 Sep 2019	Early onset or syndromic epilepsy v1.274	CACNA1D	Rebecca Foulger Marked gene: CACNA1D as ready
07 Sep 2019	Early onset or syndromic epilepsy v1.274	CACNA1D	Rebecca Foulger Gene: cacna1d has been classified as Green List (High Evidence).
07 Sep 2019	Early onset or syndromic epilepsy v1.274	CACNA1D	Rebecca Foulger Added comment: Comment on mode of inheritance: Kept Mode of Inheritance as 'BOTH monoallelic and biallelic' based on post-Webex review from Helen Lord.
07 Sep 2019	Early onset or syndromic epilepsy v1.274	CACNA1D	Rebecca Foulger Mode of inheritance for gene: CACNA1D was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
07 Sep 2019	Early onset or syndromic epilepsy v1.273	ATRX	Rebecca Foulger Marked gene: ATRX as ready
07 Sep 2019	Early onset or syndromic epilepsy v1.273	ATRX	Rebecca Foulger Gene: atrx has been classified as Green List (High Evidence).
07 Sep 2019	Early onset or syndromic epilepsy v1.273	ATRX	Rebecca Foulger Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome; Mental retardation-hypotonic facies syndrome, X-linked to Alpha-thalassemia/mental retardation syndrome, 301040; Mental retardation-hypotonic facies syndrome, X-linked, 309580
07 Sep 2019	Early onset or syndromic epilepsy v1.272	PIGP	Konstantinos Varvagiannis gene: PIGP was added gene: PIGP was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: PIGP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIGP were set to 28334793; 31139695 Phenotypes for gene: PIGP were set to Generalized hypotonia; Global developmental delay; Seizures; Intellectual disability; Feeding difficulties; Cortical visual impairment Penetrance for gene: PIGP were set to Complete Review for gene: PIGP was set to GREEN Added comment: Johnstone et al. (2017 - PMID: 28334793) report on 2 sibs born to non-consanguineous parents of French-Irish ancestry. Both presented with seizures (onset at the age of 2 and 7 weeks respectively), hypotonia and profound DD. Other features included CVI and feeding difficulties. Extensive metabolic testing as well as prior genetic testing (ARX, STXBP1, MECP2, aCGH) in the family were non-diagnostic. WES suggested the presence of 2 PIGP variants with Sanger sequencing used for confirmation and segregation studies. PIGP encodes a subunit of the enzyme that catalyzes the first step of glycophosphatidylinositol (GPI) anchor biosynthesis. Mutations in other genes whose proteins are in complex with PIGP (PIGA, PIGC, PIGQ, PIGY, DPM2) lead to similar phenotypes. The phenotype overall was also overlapping with the inherited GPI deficiencies (belonging to the broader group of CDGs). PIGP has 2 isoforms, which differ by 24 amino acids due to utilization of alternative start codons [corresponding to NM_153681.2 (158 aa) and NM_153682.2 (134 aa)]. The variants identified affected both transcripts with the first SNV leading either to loss of the start codon (NM_153682.2:c.2T>C - p.Met1Thr) or to substitution of a methionine at position 25(NM_153681.2:c.74T>C;p.Met25Thr). The second variant led to frameshift in the last exon of both transcripts predicting a longer protein product (NM_153681.2:c.456delA / p.Glu153AsnfsTer34 or NM_153682.2:c.384delA / p.Glu129AsnfsTer34). Overall extensive studies demonstrated decreased levels of PIGP mRNA in patient fibroblast, decreased amounts of mutant protein in tranfected HEK293 cells. The decreased levels of GPI-APs further supported the effect of variants : - mRNA levels in patient fibroblasts were reduced compared to controls. Conclusions could not be drawn from Western blot, since no antibodies could specifically detect PIGP. HEK293 cells transfected of mt or wt HA-tagged PIGP cDNA led to undetectable amounts for the first variant (both M1T/M25T) and a protein product of increased molecular weight for the frameshift one. - Flow cytometry of patient granulocytes indicated reduced signal of CD16 (a GPI-anchored protein) and FLAER (binding directly to the GPI anchor). - Reduced levels of GPI-APs were also observed in PIGP deficient HAP1 cells transfected with either wt, or mutant PIGP cDNA (of both isoforms for the M1T/M25T or isoform 2 for the frameshift mutation). -------- Krenn et al. (2019 - PMID: 31139695) described a patient born to non-consanguineous Polish parents. Features were highly similar to those reported by Johnstone et al. and incl. intractable infantile seizures (onset at 7m), hypotonia, severe DD and feeding difficulties. Metabolic work-up failed to identify an alternative diagnosis. WES revealed homozygosity for the frameshift variant reported by Johnstone et al. Sanger sequencing confirmed the variant and carrier state in both parents. Identified ROH of less than 7 Mb in the WES data, suggested a founder mutation rather than unreported consanguinity. The variant is present 9 times in gnomAD (AF of 3.2e-5 / no homozygotes). Flow cytometry of patient granulocytes, revealed markedly reduced expression of GPI-APs (CD157, CD59, FLAER) compared to parents/controls. ALP was normal in all aforementioned individuals (probably in line with PIGP being involved in the 1st step of the GPI anchor biosynthesis). -------- A further individual with phenotype of EIEE-55;GPIBD-14 is reported in LOVD [Individual #00246132]. This individual, born to conanguineous parents, was tested by WES and found to be homozygous for a frameshift variant, also affecting the last exon in both transcripts (NM_153681.2:c.384delA (p.Glu129ArgfsTer7) / NM_153682.2:c.312delA (p.Glu105ArgfsTer7). This was probably in agreement with segregation studies according to the respective entry. The specific variant is reported as pathogenic [variant ID #0000500090]. -------- ?Epileptic encephalopathy, early infantile, 55 (MIM 617599) is the corresponding phenotype in OMIM. There is no relevant G2P entry. PIGP is included in gene panels for ID offered by some diagnostic laboratories (eg. GeneDx). -------- As a result, PIGP can be considered for inclusion in the ID/epilepsy panels probably as green (3 individuals, role of the gene and similarity to other inherited GPI deficiencies, extensive supporting studies) or amber. (Please consider inclusion in other possibly relevant panels eg. CDGs, etc). Sources: Literature
07 Sep 2019	Early onset or syndromic epilepsy v1.272	ATRX	Rebecca Foulger Added comment: Comment on mode of inheritance: Updated Mode of Inheritance from XLR to XLD based on Post-Webex review by Helen Lord.
07 Sep 2019	Early onset or syndromic epilepsy v1.272	ATRX	Rebecca Foulger Mode of inheritance for gene: ATRX was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
07 Sep 2019	Early onset or syndromic epilepsy v1.271	ATRX	Rebecca Foulger Publications for gene: ATRX were set to 25606380; 11449489; 7697714; 11050622
07 Sep 2019	Early onset or syndromic epilepsy v1.270	ARHGEF9	Rebecca Foulger Marked gene: ARHGEF9 as ready
07 Sep 2019	Early onset or syndromic epilepsy v1.270	ARHGEF9	Rebecca Foulger Gene: arhgef9 has been classified as Green List (High Evidence).
07 Sep 2019	Early onset or syndromic epilepsy v1.270	ARHGEF9	Rebecca Foulger Publications for gene: ARHGEF9 were set to 21633362; 15215304
07 Sep 2019	Early onset or syndromic epilepsy v1.269	ARHGEF9	Rebecca Foulger Publications for gene: ARHGEF9 were set to
07 Sep 2019	Early onset or syndromic epilepsy v1.268	ARHGEF9	Rebecca Foulger Added comment: Comment on mode of inheritance: Updated Mode of Inheritance from XLR to XLD based on Post-Webex review by Helen Lord.
07 Sep 2019	Early onset or syndromic epilepsy v1.268	ARHGEF9	Rebecca Foulger Mode of inheritance for gene: ARHGEF9 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
07 Sep 2019	Early onset or syndromic epilepsy v1.267	TUBB2A	Rebecca Foulger Marked gene: TUBB2A as ready
07 Sep 2019	Early onset or syndromic epilepsy v1.267	TUBB2A	Rebecca Foulger Gene: tubb2a has been classified as Green List (High Evidence).
07 Sep 2019	Early onset or syndromic epilepsy v1.267	TUBB2A	Rebecca Foulger commented on gene: TUBB2A: Kept rating as Green based on post-Webex reviews from Helen Lord and Alison Callaway (West Midlands, Oxford and Wessex GLH).
07 Sep 2019	Early onset or syndromic epilepsy v1.267	SLC25A12	Rebecca Foulger Marked gene: SLC25A12 as ready
07 Sep 2019	Early onset or syndromic epilepsy v1.267	SLC25A12	Rebecca Foulger Gene: slc25a12 has been classified as Green List (High Evidence).
07 Sep 2019	Early onset or syndromic epilepsy v1.267	SLC25A12	Rebecca Foulger commented on gene: SLC25A12: Kept rating as Green based on post-Webex reviews from Helen Lord and Alison Callaway.
07 Sep 2019	Early onset or syndromic epilepsy v1.267	SLC25A12	Rebecca Foulger Publications for gene: SLC25A12 were set to 24515575; 19641205; 27290639
07 Sep 2019	Early onset or syndromic epilepsy v1.266	KCNMA1	Rebecca Foulger Marked gene: KCNMA1 as ready
07 Sep 2019	Early onset or syndromic epilepsy v1.266	KCNMA1	Rebecca Foulger Gene: kcnma1 has been classified as Green List (High Evidence).
07 Sep 2019	Early onset or syndromic epilepsy v1.266	KCNMA1	Rebecca Foulger Classified gene: KCNMA1 as Green List (high evidence)
07 Sep 2019	Early onset or syndromic epilepsy v1.266	KCNMA1	Rebecca Foulger Added comment: Comment on list classification: Updated rating of KCNMA1 from Amber to Green based on post-Webex reviews from Helen Lord, Allison Callaway and Konstantinos Varvagiannis.
07 Sep 2019	Early onset or syndromic epilepsy v1.266	KCNMA1	Rebecca Foulger Gene: kcnma1 has been classified as Green List (High Evidence).
07 Sep 2019	Early onset or syndromic epilepsy v1.265	KCNMA1	Rebecca Foulger Added comment: Comment on mode of inheritance: Kept Mode of Inheritance as 'BOTH monoallelic and biallelic' based on post-Webex reviews from Helen Lord and Konstantinos Varvagiannis.
07 Sep 2019	Early onset or syndromic epilepsy v1.265	KCNMA1	Rebecca Foulger Mode of inheritance for gene: KCNMA1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
07 Sep 2019	Early onset or syndromic epilepsy v1.264	ALPL	Rebecca Foulger commented on gene: ALPL: Kept rating as Green based on post-Webex reviews from Helen Lord and Alison Callaway.
07 Sep 2019	Early onset or syndromic epilepsy v1.264	ALPL	Rebecca Foulger changed review comment from: Comment on mode of inheritance: Updated Mode of Inheritance from 'BOTH monoallelic and biallelic to 'BIALLELIC' based on Post-Webex review by Helen Lord: AR but not AD Hypophosphatasia associated with seizures.; to: Comment on mode of inheritance: Updated Mode of Inheritance from 'BOTH monoallelic and biallelic' to 'BIALLELIC' based on Post-Webex review by Helen Lord: AR but not AD Hypophosphatasia is associated with seizures.
07 Sep 2019	Early onset or syndromic epilepsy v1.264	ALPL	Rebecca Foulger Added comment: Comment on mode of inheritance: Updated Mode of Inheritance from 'BOTH monoallelic and biallelic to 'BIALLELIC' based on Post-Webex review by Helen Lord: AR but not AD Hypophosphatasia associated with seizures.
07 Sep 2019	Early onset or syndromic epilepsy v1.264	ALPL	Rebecca Foulger Mode of inheritance for gene: ALPL was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
06 Sep 2019	Early onset or syndromic epilepsy v1.263	H3F3B	Louise Daugherty Tag new-gene-name tag was added to gene: H3F3B.
06 Sep 2019	Early onset or syndromic epilepsy v1.263	H3F3B	Louise Daugherty commented on gene: H3F3B
06 Sep 2019	Early onset or syndromic epilepsy v1.263	H3F3A	Louise Daugherty Tag new-gene-name tag was added to gene: H3F3A.
06 Sep 2019	Early onset or syndromic epilepsy v1.263	H3F3A	Louise Daugherty commented on gene: H3F3A
06 Sep 2019	Early onset or syndromic epilepsy v1.263	KIF1BP	Louise Daugherty Tag new-gene-name tag was added to gene: KIF1BP.
06 Sep 2019	Early onset or syndromic epilepsy v1.263	KIF1BP	Louise Daugherty commented on gene: KIF1BP: Added new-gene-name tag, new approved HGNC gene symbol for KIF1BP is KIFBP
06 Sep 2019	Early onset or syndromic epilepsy v1.263	VARS	Louise Daugherty Tag new-gene-name tag was added to gene: VARS.
06 Sep 2019	Early onset or syndromic epilepsy v1.263	VARS	Louise Daugherty commented on gene: VARS
06 Sep 2019	Early onset or syndromic epilepsy v1.263	QARS	Louise Daugherty Tag new-gene-name tag was added to gene: QARS.
06 Sep 2019	Early onset or syndromic epilepsy v1.263	QARS	Louise Daugherty commented on gene: QARS
06 Sep 2019	Early onset or syndromic epilepsy v1.263	KARS	Louise Daugherty Tag new-gene-name tag was added to gene: KARS.
06 Sep 2019	Early onset or syndromic epilepsy v1.263	KARS	Louise Daugherty commented on gene: KARS
06 Sep 2019	Early onset or syndromic epilepsy v1.263	AARS	Louise Daugherty Tag new-gene-name tag was added to gene: AARS.
06 Sep 2019	Early onset or syndromic epilepsy v1.263	AARS	Louise Daugherty commented on gene: AARS
05 Sep 2019	Early onset or syndromic epilepsy v1.263	KCNA1	Rebecca Foulger Source North West GLH was added to KCNA1.
05 Sep 2019	Early onset or syndromic epilepsy v1.263	SCN9A	Rebecca Foulger Source North West GLH was added to SCN9A.
05 Sep 2019	Early onset or syndromic epilepsy v1.263	FLNA	Rebecca Foulger Source North West GLH was added to FLNA.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	KCNA1	Rebecca Foulger commented on gene: KCNA1: Diane Cairns (Manchester University NHS, North West GLH) comments that "I have looked into the variants that we found on our Epilepsy panel in the FLNA, SCN9A and KCNA1 genes. Using ACGS guidelines these variants are all Class 3 or below, we therefore feel that it would be acceptable to remove these genes from the Epilepsy Panel." (personal communication via email to Jane Deller, 2019-09-04)
05 Sep 2019	Early onset or syndromic epilepsy v1.262	SCN9A	Rebecca Foulger commented on gene: SCN9A: Diane Cairns (Manchester University NHS, North West GLH) comments that "I have looked into the variants that we found on our Epilepsy panel in the FLNA, SCN9A and KCNA1 genes. Using ACGS guidelines these variants are all Class 3 or below, we therefore feel that it would be acceptable to remove these genes from the Epilepsy Panel." (personal communication via email to Jane Deller, 2019-09-04)
05 Sep 2019	Early onset or syndromic epilepsy v1.262	FLNA	Rebecca Foulger commented on gene: FLNA: Diane Cairns (Manchester University NHS, North West GLH) comments that "I have looked into the variants that we found on our Epilepsy panel in the FLNA, SCN9A and KCNA1 genes. Using ACGS guidelines these variants are all Class 3 or below, we therefore feel that it would be acceptable to remove these genes from the Epilepsy Panel." (personal communication via email to Jane Deller, 2019-09-04)
05 Sep 2019	Early onset or syndromic epilepsy v1.262	ARHGEF9	Rebecca Foulger commented on gene: ARHGEF9: Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	SLC16A2	Rebecca Foulger commented on gene: SLC16A2: Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	PIGA	Rebecca Foulger commented on gene: PIGA: Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	MED12	Rebecca Foulger commented on gene: MED12: Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	MAGI2	Rebecca Foulger commented on gene: MAGI2: Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	IDH2	Rebecca Foulger commented on gene: IDH2: Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded an Amber rating to match the original West Midlands, Oxford and Wessex GLH rating.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	CACNA1D	Rebecca Foulger commented on gene: CACNA1D: Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	NRXN1	Rebecca Foulger commented on gene: NRXN1: Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	SLC35A2	Rebecca Foulger commented on gene: SLC35A2: Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	SLC1A2	Rebecca Foulger commented on gene: SLC1A2: Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	SLC12A5	Rebecca Foulger commented on gene: SLC12A5: Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	IKBKG	Rebecca Foulger commented on gene: IKBKG: Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	HEPACAM	Rebecca Foulger commented on gene: HEPACAM: Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	DEAF1	Rebecca Foulger commented on gene: DEAF1: Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	ATRX	Rebecca Foulger commented on gene: ATRX: Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	GRIA2	Rebecca Foulger edited their review of gene: GRIA2: Added comment: Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene was added to the Genetic epilepsy syndromes panel after the initial panel was reviewed by West Midlands, Oxford and Wessex GLH: this gene was therefore reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.; Changed rating: AMBER
05 Sep 2019	Early onset or syndromic epilepsy v1.262	KMT5B	Rebecca Foulger reviewed gene: KMT5B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	KCNH5	Rebecca Foulger reviewed gene: KCNH5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	KCND2	Rebecca Foulger reviewed gene: KCND2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	CSNK2A1	Rebecca Foulger commented on gene: CSNK2A1: Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene was added to the Genetic epilepsy syndromes panel after the initial panel was reviewed by West Midlands, Oxford and Wessex GLH: this gene was therefore reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	BCORL1	Rebecca Foulger edited their review of gene: BCORL1: Added comment: Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene was added to the Genetic epilepsy syndromes panel after the initial panel was reviewed by West Midlands, Oxford and Wessex GLH: this gene was therefore reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.; Changed rating: AMBER
05 Sep 2019	Early onset or syndromic epilepsy v1.262	ZNF142	Rebecca Foulger reviewed gene: ZNF142: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	ZMIZ1	Rebecca Foulger reviewed gene: ZMIZ1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	USP7	Rebecca Foulger edited their review of gene: USP7: Added comment: Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene was added to the Genetic epilepsy syndromes panel after the initial panel was reviewed by West Midlands, Oxford and Wessex GLH: this gene was therefore reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.; Changed rating: AMBER
05 Sep 2019	Early onset or syndromic epilepsy v1.262	TRRAP	Rebecca Foulger edited their review of gene: TRRAP: Added comment: Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene was added to the Genetic epilepsy syndromes panel after the initial panel was reviewed by West Midlands, Oxford and Wessex GLH: this gene was therefore reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.; Changed rating: AMBER
05 Sep 2019	Early onset or syndromic epilepsy v1.262	TRPM3	Rebecca Foulger edited their review of gene: TRPM3: Added comment: Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene was added to the Genetic epilepsy syndromes panel after the initial panel was reviewed by West Midlands, Oxford and Wessex GLH: this gene was therefore reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.; Changed rating: AMBER
05 Sep 2019	Early onset or syndromic epilepsy v1.262	SLC35A3	Rebecca Foulger edited their review of gene: SLC35A3: Added comment: Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene was added to the Genetic epilepsy syndromes panel after the initial panel was reviewed by West Midlands, Oxford and Wessex GLH: this gene was therefore reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.; Changed rating: AMBER
05 Sep 2019	Early onset or syndromic epilepsy v1.262	RNF13	Rebecca Foulger reviewed gene: RNF13: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	PAK1	Rebecca Foulger reviewed gene: PAK1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	NUS1	Rebecca Foulger reviewed gene: NUS1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	LSS	Rebecca Foulger reviewed gene: LSS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	FUK	Rebecca Foulger reviewed gene: FUK: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	CLCN6	Rebecca Foulger reviewed gene: CLCN6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	AIMP2	Rebecca Foulger reviewed gene: AIMP2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	AFF3	Rebecca Foulger edited their review of gene: AFF3: Added comment: Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene was added to the Genetic epilepsy syndromes panel after the initial panel was reviewed by West Midlands, Oxford and Wessex GLH: this gene was therefore reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.; Changed rating: AMBER
05 Sep 2019	Early onset or syndromic epilepsy v1.262	POLG	Rebecca Foulger commented on gene: POLG: Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene was added to the Genetic epilepsy syndromes panel after the initial panel was reviewed by West Midlands, Oxford and Wessex GLH: this gene was therefore reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	ZDHHC9	Rebecca Foulger reviewed gene: ZDHHC9: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	WARS2	Rebecca Foulger reviewed gene: WARS2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	VPS11	Rebecca Foulger reviewed gene: VPS11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	VAMP2	Rebecca Foulger reviewed gene: VAMP2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	SNAP25	Rebecca Foulger reviewed gene: SNAP25: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	SMARCC2	Rebecca Foulger edited their review of gene: SMARCC2: Added comment: Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene was added to the Genetic epilepsy syndromes panel after the initial panel was reviewed by West Midlands, Oxford and Wessex GLH: this gene was therefore reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.; Changed rating: AMBER
05 Sep 2019	Early onset or syndromic epilepsy v1.262	PPP2CA	Rebecca Foulger reviewed gene: PPP2CA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	PIGB	Rebecca Foulger reviewed gene: PIGB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	PARS2	Rebecca Foulger reviewed gene: PARS2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	P4HTM	Rebecca Foulger reviewed gene: P4HTM: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	NBEA	Rebecca Foulger reviewed gene: NBEA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	KMT2E	Rebecca Foulger reviewed gene: KMT2E: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	KCNT2	Rebecca Foulger reviewed gene: KCNT2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	DHPS	Rebecca Foulger reviewed gene: DHPS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	DEGS1	Rebecca Foulger edited their review of gene: DEGS1: Added comment: Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene was added to the Genetic epilepsy syndromes panel after the initial panel was reviewed by West Midlands, Oxford and Wessex GLH: this gene was therefore reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.; Changed rating: AMBER
05 Sep 2019	Early onset or syndromic epilepsy v1.262	CTNNA2	Rebecca Foulger reviewed gene: CTNNA2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	CACNA1B	Rebecca Foulger reviewed gene: CACNA1B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	ATN1	Rebecca Foulger reviewed gene: ATN1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	AP2M1	Rebecca Foulger reviewed gene: AP2M1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	ALKBH8	Rebecca Foulger reviewed gene: ALKBH8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
05 Sep 2019	Early onset or syndromic epilepsy v1.262	ACTL6B	Rebecca Foulger edited their review of gene: ACTL6B: Added comment: Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene was added to the Genetic epilepsy syndromes panel after the initial panel was reviewed by West Midlands, Oxford and Wessex GLH: this gene was therefore reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.; Changed rating: AMBER
05 Sep 2019	Early onset or syndromic epilepsy v1.262	ALPL	Rebecca Foulger commented on gene: ALPL: Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset that were re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	EMX2	Rebecca Foulger commented on gene: EMX2: Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset that were re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	NPRL2	Rebecca Foulger commented on gene: NPRL2: Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset that were re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	KCNMA1	Rebecca Foulger commented on gene: KCNMA1: Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset that were re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	TUBB2A	Rebecca Foulger commented on gene: TUBB2A: Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset that were re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	SLC25A12	Rebecca Foulger commented on gene: SLC25A12: Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset that were re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.
05 Sep 2019	Early onset or syndromic epilepsy v1.262	HCN2	Rebecca Foulger commented on gene: HCN2: Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset that were re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.
05 Sep 2019	Early onset or syndromic epilepsy v1.261	ARHGEF9	Helen Lord reviewed gene: ARHGEF9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
05 Sep 2019	Early onset or syndromic epilepsy v1.261	SLC16A2	Helen Lord reviewed gene: SLC16A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
05 Sep 2019	Early onset or syndromic epilepsy v1.261	PIGA	Helen Lord reviewed gene: PIGA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
05 Sep 2019	Early onset or syndromic epilepsy v1.261	MED12	Helen Lord reviewed gene: MED12: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
05 Sep 2019	Early onset or syndromic epilepsy v1.261	MAGI2	Helen Lord reviewed gene: MAGI2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	IDH2	Helen Lord reviewed gene: IDH2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	CACNA1D	Helen Lord reviewed gene: CACNA1D: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	NRXN1	Helen Lord reviewed gene: NRXN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	SLC35A2	Helen Lord reviewed gene: SLC35A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
05 Sep 2019	Early onset or syndromic epilepsy v1.261	SLC1A2	Helen Lord reviewed gene: SLC1A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	SLC12A5	Helen Lord reviewed gene: SLC12A5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	IKBKG	Helen Lord reviewed gene: IKBKG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
05 Sep 2019	Early onset or syndromic epilepsy v1.261	HEPACAM	Helen Lord reviewed gene: HEPACAM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	DEAF1	Helen Lord reviewed gene: DEAF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	ATRX	Helen Lord reviewed gene: ATRX: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
05 Sep 2019	Early onset or syndromic epilepsy v1.261	GRIA2	Helen Lord reviewed gene: GRIA2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	KMT5B	Helen Lord reviewed gene: KMT5B: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	KCNH5	Helen Lord reviewed gene: KCNH5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	KCND2	Helen Lord reviewed gene: KCND2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	CSNK2A1	Helen Lord reviewed gene: CSNK2A1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	BCORL1	Helen Lord reviewed gene: BCORL1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
05 Sep 2019	Early onset or syndromic epilepsy v1.261	ZNF142	Helen Lord reviewed gene: ZNF142: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	ZMIZ1	Helen Lord reviewed gene: ZMIZ1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	USP7	Helen Lord reviewed gene: USP7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	TRRAP	Helen Lord reviewed gene: TRRAP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	TRPM3	Helen Lord reviewed gene: TRPM3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	SLC35A3	Helen Lord reviewed gene: SLC35A3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	RNF13	Helen Lord reviewed gene: RNF13: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	PAK1	Helen Lord reviewed gene: PAK1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	NUS1	Helen Lord reviewed gene: NUS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	LSS	Helen Lord reviewed gene: LSS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	FUK	Helen Lord reviewed gene: FUK: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	CLCN6	Helen Lord reviewed gene: CLCN6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	AIMP2	Helen Lord reviewed gene: AIMP2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	AFF3	Helen Lord reviewed gene: AFF3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	POLG	Helen Lord reviewed gene: POLG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	ZDHHC9	Helen Lord reviewed gene: ZDHHC9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
05 Sep 2019	Early onset or syndromic epilepsy v1.261	WARS2	Helen Lord reviewed gene: WARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	VPS11	Helen Lord reviewed gene: VPS11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	VAMP2	Helen Lord reviewed gene: VAMP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	SNAP25	Helen Lord reviewed gene: SNAP25: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	SMARCC2	Helen Lord reviewed gene: SMARCC2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	PPP2CA	Helen Lord reviewed gene: PPP2CA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	PIGB	Helen Lord reviewed gene: PIGB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	PARS2	Helen Lord reviewed gene: PARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	P4HTM	Helen Lord reviewed gene: P4HTM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	NBEA	Helen Lord reviewed gene: NBEA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	KMT2E	Helen Lord reviewed gene: KMT2E: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	KCNT2	Helen Lord reviewed gene: KCNT2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	DHPS	Helen Lord reviewed gene: DHPS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	DEGS1	Helen Lord reviewed gene: DEGS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	CTNNA2	Helen Lord reviewed gene: CTNNA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	CACNA1B	Helen Lord reviewed gene: CACNA1B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	ATN1	Helen Lord reviewed gene: ATN1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	AP2M1	Helen Lord reviewed gene: AP2M1: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	ALKBH8	Helen Lord reviewed gene: ALKBH8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	ACTL6B	Helen Lord reviewed gene: ACTL6B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	ALPL	Helen Lord reviewed gene: ALPL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	EMX2	Helen Lord reviewed gene: EMX2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	NPRL2	Helen Lord reviewed gene: NPRL2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
05 Sep 2019	Early onset or syndromic epilepsy v1.261	KCNMA1	Helen Lord reviewed gene: KCNMA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	TUBB2A	Helen Lord reviewed gene: TUBB2A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
05 Sep 2019	Early onset or syndromic epilepsy v1.261	SLC25A12	Helen Lord reviewed gene: SLC25A12: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
05 Sep 2019	Early onset or syndromic epilepsy v1.261	HCN2	Helen Lord reviewed gene: HCN2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
31 Aug 2019	Early onset or syndromic epilepsy v1.260	KATNB1	Konstantinos Varvagiannis gene: KATNB1 was added gene: KATNB1 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: KATNB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KATNB1 were set to 25521378; 25521379; 26640080 Phenotypes for gene: KATNB1 were set to Lissencephaly 6, with microcephaly (MIM 616212) Review for gene: KATNB1 was set to GREEN Added comment: Biallelic pathogenic KATNB1 variants cause Lissencephaly 6, with microcephaly (MIM 616212). At least 13 affected individuals from 9 (mostly consanguineous) families have probably been reported in the following articles: - Mishra-Gorur et al. (2014 - PMID: 25521378) [7 individuals from 5 unrelated families] - Hu et al. (2014 - PMID: 25521379) [5 individuals from 3 families] - Yigit el al. (2016 - PMID: 26640080) [1 subject born to consanguineous parents] Seizures can be part of the phenotype (although not universal / reported in all 3 studies in several families). Several different variants have been reported to date. Extensive studies as for the impact of mutations at the cellular level as well as animal models (zebrafish, mouse, drosophila) support involvement of KATNB1. These arguments, provided mainly by the first two studies, are summarized in the respective OMIM entry for the disorder : https://omim.org/entry/616212 (variants and their effect are discussed in the entry for KATNB1 - https://omim.org/entry/602703). The individual reported by Yigit el al. was a 5 year-old girl with - among others - severely delayed psychomotor development and seizures. The child was found to harbor a homozygous splice site variant (removing the acceptor AG signature). Confirmation of the variant and segregation studies were performed with Sanger sequencing. cDNA studies were carried out and demonstrated aberrant splicing. KATNB1 is not associated with any disorder in G2P. The gene is included in panels for ID offered by several diagnostic laboratories (incl. Radboudumc). As a result, this gene can be considered for inclusion in the current panel probably as green (or amber). Sources: Literature
31 Aug 2019	Early onset or syndromic epilepsy v1.260	PAK1	Konstantinos Varvagiannis edited their review of gene: PAK1: Added comment: Based on a further recent study, PAK1 can probably be upgraded to green in both ID and epilepsy gene panels: Horn et al. (2019 - doi.org/10.1093/brain/awz264) report on 4 additional individuals with de novo missense PAK1 pathogenic variants. ID, seizures and macrocephaly and walking difficulties were observed in all (4/4). ASD was reported in 3 (but was not among the features in the study by Harms et al). PAK1 encodes p21 protein-activated kinase 1. The protein has 2 major domains, an autoregulatory and a protein kinase domain. Homodimerization masks the active site of the kinase, leading to autoinhibition (inactive form). PAK1 is activated by dissociation into monomers upon binding of the GTP-bound forms of the Rho GTPases CDC42 and RAC1. TRIO and HACE1 are indirect regulators of PAK1, via RAC1. PAK1 in turn, activates LIMK1 which plays a critical role in dendritic spine morphogenesis and brain function. CDC42, RAC1, TRIO, HACE1 are all associated with neurodevelopmental disorders. Activation of RAC-PAK1-LIMK1 pathway has been demonstrated for Fragile-X syndrome (sharing ID, macrocephaly and seizures). Mutations in PAK3, another member of the group I PAK subfamily with similar activation mechanism to PAK1 (by CDC42 / RAC1), cause Mental retardation, X-linked 30/47 (MIM 300558) (Green rating in the current panel). 4 additional missense variants - further to the 2 previously described ones - were found, all as de novo events: c.397T>C (p.Ser133Pro) / c.361C>T p.(Pro121Ser) / c.328T>A p.(Ser110Thr) / c.1409T>G (p.Leu470Arg) [For the specific variants, cDNA and aa change are the same for both NM_001128620.1 and NM_002576]. The 3 former variants located within the autoinhibitory domain while the latter in the protein kinase domain though - again - close to the autoinhibitory one (in tertiary structure). A gain of function effect by reduced ability of autoinhibition (leading to autophosphorylation) and activation of PAK1 is the suggested mechanism. Gain of function is also supported by the fact that Pak1-/- do not exhibit neurodevelopmental anomalies / abnormal head size. PAK1 is not particularly intolerant to LoF variants as suggested by its pLI of 0.67. The corresponding phenotype in OMIM is Intellectual developmental disorder with macrocephaly, seizures, and speech delay (MIM 618158). The gene is part of the DD panel of G2P, associated with "Neurodevelopmental Disorder" (monoallelic, activating / disease confidence : probable). PAK1 is included in the gene panel for ID offered by Radboudumc. (Previous review below); Changed rating: GREEN; Changed publications: 30290153, doi.org/10.1093/brain/awz264
29 Aug 2019	Early onset or syndromic epilepsy v1.260	GABBR2	Rebecca Foulger Phenotypes for gene: GABBR2 were changed from EPILEPTIC ENCEPHALOPATHY; Rett syndrome to EPILEPTIC ENCEPHALOPATHY; Rett syndrome; Epileptic encephalopathy, early infantile, 59, 617904
28 Aug 2019	Early onset or syndromic epilepsy v1.259	GOT2	Catherine Snow Tag treatable tag was added to gene: GOT2. Tag watchlist tag was added to gene: GOT2.
28 Aug 2019	Early onset or syndromic epilepsy v1.259	GOT2	Catherine Snow Classified gene: GOT2 as Amber List (moderate evidence)
28 Aug 2019	Early onset or syndromic epilepsy v1.259	GOT2	Catherine Snow Gene: got2 has been classified as Amber List (Moderate Evidence).
28 Aug 2019	Early onset or syndromic epilepsy v1.258	GOT2	Catherine Snow reviewed gene: GOT2: Rating: AMBER; Mode of pathogenicity: None; Publications: 31422819; Phenotypes: Global developmental delay, Intellectual disability, Seizures; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
27 Aug 2019	Early onset or syndromic epilepsy v1.258	ALPL	Rebecca Foulger changed review comment from: PMID:30979546: Whyte et al., 2019 report Vitamin B6-dependent seizures in 10/38 (26%) of patients: 7 patients had documented seizures and 3 patients had a family hisotry of seizures based upon medical records.; to: PMID:30979546: Whyte et al., 2019 report Vitamin B6-dependent seizures in 10/38 (26%) of patients: 7 patients had documented seizures and 3 patients had a family history of seizures based upon medical records.
27 Aug 2019	Early onset or syndromic epilepsy v1.258	TRRAP	Rebecca Foulger Publications for gene: TRRAP were set to 30827496
27 Aug 2019	Early onset or syndromic epilepsy v1.257	TRRAP	Rebecca Foulger Added comment: Comment on phenotypes: MIM:603015 is the gene identifier. Therefore updated OMIM phenotype to the disorder identifier (618454) as per Alison Callaway's review.
27 Aug 2019	Early onset or syndromic epilepsy v1.257	TRRAP	Rebecca Foulger Phenotypes for gene: TRRAP were changed from Microcephaly; Seizures; Abnormal heart morphology; Autism; Developmental delay with or without dysmorphic facies and autism, 603015; Intellectual disability; Abnormality of the urinary system; Global developmental delay to Microcephaly; Seizures; Abnormal heart morphology; Autism; Developmental delay with or without dysmorphic facies and autism, 618454; Intellectual disability; Abnormality of the urinary system; Global developmental delay
25 Aug 2019	Early onset or syndromic epilepsy v1.256	KCNMA1	Konstantinos Varvagiannis changed review comment from: In a recent extensive review of the literature, Bailey et al. (2019 - PMID: 31427379) summarize the phenotype of KCNMA1-related channelopathy. Overall the features of 37 subjects with 16 KCNMA1 pathogenic variants are discussed in detail. [An also relevant report by Liang et al. published in 6/2019 - PMID: 31152168 - was also considered for this review]. KCNMA1 encodes the pore-forming α subunit of large-conductance voltage- and Ca(2+)-activated K+ channel (also called BK channel). BK channels have highest expression levels in brain (acting as regulators of neuronal exciatbility) and muscle. Variants in the review are distinguished in GoF, LoF and VUS (the latter used for variants of unknown/uncharacterized effect on BK channel activity) [NM_002247.3 mentioned as RefSeq]: - GoF variants included D434G (a variant reported in 13 individuals) and N995S (also reported as N999S or N1053S). - LoF variants included S351Y, G356R, G375R, N449fs, I663V, C413Y, P805L, D984N, G354S. - Uncharacterized variants included R458Ter, Y676Lfs7 (both presumed to result to LoF), K518N, E656A, N1195S, E884K. The disorder exhibited in most cases aut. dominant inheritance (either as de novo occurrence of a variant or identification in successive generations), with autosomal recessive inheritance reported in one pedigree (sibs with Y676Lfsfs) (Tabarki et al. 2016 - PMID: 27567911). As the authors comment, the hallmark of KCNMA1-related channelopathy is neurological dysfunction incl. seizures, movement disorders, DD and ID. Epilepsy was a feature in approx. half individuals (18/37) irrespective of mutation type (eg. 9/20 in the case of GoF, 6/13 in LoF variants). Seizure characteristics were highly variable as for the onset, type, EEG pattern, frequency/duration and response to medication. Overlapping types were noted for GoF and LoF mutations incl. myoclonic, GTCS, absence seizures with few being more frequent or specific in certain mutation types. Individuals with the same variant may present or not certain features eg. 6/13 members of a large family with D434G or 3/7 (all unrelated) individuals with N1053S developed epilepsy. Animal studies support a role for both LoF and GoF alterations in BK channel activity as for the seizures, with more solid evidence/correlation with GoF mutations. (Other phenotypes eg. movement disorders are also supported by animal models). Similarly developmental delay has been reported in 21/37 individuals and intellectual disability in 12/37 (both GoF and LoF) with severe presentation in certain cases (eg. in 3 individuals with G375R) while on several occasions severity (or presence of this feature(?)) has probably not been commented on. The KCNMA1-related disorders in OMIM are the following: ?Cerebellar atrophy, developmental delay, and seizures, 617643 (AR) Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy, 609446 (AD) KCNMA1 is part of the DD panel of G2P associated with Generalized epilepsy and paroxysmal dyskinesia (monoallelic, activating mutations / disease confidence : possible). KCNMA1 is included in several gene panels for epilepsy incl. those of Radboudumc and Victorian Clinical Genetics and several other panels summarized in the supplement of the review. The gene is included in gene panels for ID offered by some diagnostic laboratories (eg. GeneDx). As a result upgrade to green rating can be considered for the epilepsy panel. The gene could possibly be upgraded to amber (or green) in the ID panel, too.; to: In a recent extensive review of the literature, Bailey et al. (2019 - PMID: 31427379) summarize the phenotype of KCNMA1-related channelopathy. Overall the features of 37 subjects with 16 KCNMA1 pathogenic variants are discussed in detail. [An also relevant report by Liang et al. published in 6/2019 - PMID: 31152168 - was also considered for this review]. KCNMA1 encodes the pore-forming α subunit of large-conductance voltage- and Ca(2+)-activated K+ channel (also called BK channel). BK channels have highest expression levels in brain (acting as regulators of neuronal exciatbility) and muscle. Variants in the review are distinguished in GoF, LoF and VUS (the latter used for variants of unknown/uncharacterized effect on BK channel activity) [NM_002247.3 mentioned as RefSeq]: - GoF variants included D434G (a variant reported in 13 individuals) and N995S (also reported as N999S or N1053S). - LoF variants included S351Y, G356R, G375R, N449fs, I663V, C413Y, P805L, D984N, G354S. - Uncharacterized variants included R458Ter, Y676Lfs7 (both presumed to result to LoF), K518N, E656A, N1195S, E884K. The disorder exhibited in most cases aut. dominant inheritance (either as de novo occurrence of a variant or identification in successive generations), with autosomal recessive inheritance reported in one pedigree (sibs with Y676Lfsfs) (Tabarki et al. 2016 - PMID: 27567911). As the authors comment, the hallmark of KCNMA1-related channelopathy is neurological dysfunction incl. seizures, movement disorders, DD and ID. Epilepsy was a feature in approx. half individuals (18/37) irrespective of mutation type (eg. 9/20 in the case of GoF, 6/13 in LoF variants). Seizure characteristics were highly variable as for the onset, type, EEG pattern, frequency/duration and response to medication. Overlapping types were noted for GoF and LoF mutations incl. myoclonic, GTCS, absence seizures with few being more frequent or specific in certain mutation types. Individuals with the same variant may present or not certain features eg. 6/13 members of a large family with D434G or 3/7 (all unrelated) individuals with N1053S developed epilepsy. Animal studies support a role for both LoF and GoF alterations in BK channel activity as for the seizures, with more solid evidence/correlation with GoF mutations. (Other phenotypes eg. movement disorders are also supported by animal models). Similarly developmental delay has been reported in 21/37 individuals and intellectual disability in 12/37 (both GoF and LoF) with severe presentation in certain cases (eg. in 3 individuals with G375R) while on several occasions severity (or presence of this feature(?)) has probably not been commented on. The KCNMA1-related disorders in OMIM are the following : ?Cerebellar atrophy, developmental delay, and seizures, 617643 (AR) Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy, 609446 (AD) KCNMA1 is part of the DD panel of G2P associated with Generalized epilepsy and paroxysmal dyskinesia (monoallelic, activating mutations / disease confidence : possible). KCNMA1 is included in several gene panels for epilepsy incl. those of Radboudumc and Victorian Clinical Genetics and several other panels summarized in the supplement of the review. The gene is included in gene panels for ID offered by some diagnostic laboratories (eg. GeneDx). As a result upgrade to green rating can be considered for the epilepsy panel. The gene could possibly be upgraded to amber (or green) in the ID panel, too.
25 Aug 2019	Early onset or syndromic epilepsy v1.256	HNRNPR	Konstantinos Varvagiannis gene: HNRNPR was added gene: HNRNPR was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: HNRNPR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HNRNPR were set to 31079900; 26795593 Phenotypes for gene: HNRNPR were set to Global developmental delay; Intellectual disability; Seizures; Postnatal microcephaly; Short digit Penetrance for gene: HNRNPR were set to unknown Review for gene: HNRNPR was set to AMBER Added comment: Duijkers et al. (2019 - PMID: 31079900) report on the phenotype of 4 individuals with de novo HNRNPR variants and provide additional information on a previously published case (Helbig et al, 2016 - PMID: 26795593). All 5 were unrelated. The phenotype consisted of DD (5/5 - moderate to severe in 4 for which this has been commented on), postnatal microcephaly, seizures (4/5), brachydactyly, with additional (cardiac, urogenital, etc) anomalies observed in few. Some partially overlapping facial features were also noted. 3 truncating variants as well as a missense one, all localizing within the last exon of the gene (NM_001102398.2 used as ref. although this exon is shared by all transcripts). HNRNPR encodes heterogeneous nuclear ribonucleoprotein R, which is part of the spliceosome C. The latter functions in the nucleus to process and transport mRNA. Apart from splicing hnRNPs are also involved in other levels of gene regulation (PMID: 27215579). Some hnRNPs have been found in the cytoplasm in stress granules, aggregations of protein, RNAs and stalled initiation complexes that are formed as stress response upon oxidative insult and dissipate upon cessation of this insult. Western blot in LCLs from affected individuals demonstrated the presence of the truncated protein as well as the full-length and short isoform (as expected by the variant localization). As the C-terminal part has features of a "prion-like domain" (PrLD), critical for the formation of stress granules in the case of hnRNP-related disorders, comparison of fibroblasts from affected and healthy individuals revealed abnormal persistence of these granules in affected individuals following a recovery period, despite similar formation either at basal levels or under conditions of stress. In line with a role of hnRNPs in splicing and gene regulation, RNA-Sequencing in fibroblasts from 2 affected individuals revealed abnormal splicing of some genes (eg. HOXA5, HOXB3, LHX9) and significant dysregulation of genes important for the development (upregulation of FOXG1, TBX1, several members of the HOX family and downregulation of LHX9, IRX3, etc) possibly contributing to the patient features. Helbig et al. provide details on animal studies incl.expression in neural tissues (cerebrum and cerebellum), higher levels of expression early in the development (of both R1/R2 isoforms), etc (extensive discussion in the supplement with several articles cited). HNRNPR is not associated with any phenotype in OMIM/G2P. As a result this gene can be considered for inclusion as amber (seizures in 4/5) or green. Sources: Literature
25 Aug 2019	Early onset or syndromic epilepsy v1.256	GOT2	Konstantinos Varvagiannis gene: GOT2 was added gene: GOT2 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: GOT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GOT2 were set to 31422819 Phenotypes for gene: GOT2 were set to Global developmental delay; Intellectual disability; Seizures; Increased serum lactate; Hyperammonemia; Microcephaly; Failure to thrive; Feeding difficulties; Abnormality of nervous system morphology Penetrance for gene: GOT2 were set to Complete Review for gene: GOT2 was set to GREEN Added comment: van Karnebeek et al. (2019 - PMID: 31422819) report on 4 individuals from 3 families, with biallelic GOT2 pathogenic variants (3 missense SNVs and 1 in-frame deletion). The phenotype corresponded to a metabolic encephalopathy with onset of epilepsy in the first year of life (4/4) with DD and ID (4/4). Additional features included postnatal microcephaly, failure to thrive/feeding difficulties and cerebral anomalies (atrophy and white matter). All subjects had high blood lactate and hyperammonemia. Plasma serine was low in one case (alternative causes were ruled out). Administration of serine and pyridoxine led to clinical improvement (cessation / better control of seizures) in 2 subjects suggesting that GOT2 deficiency may be amenable to therapeutic intervention. [Treatment could not be started in the 2 further affected individuals]. GOT2 encodes the mitochondrial glutamate oxaloacetate transaminase, a component of the malate-aspartate shuttle (MAS). The latter is important for intracellular NAD(H) redox homeostasis. The authors provide several lines of evidence that GOT2 deficiency explains the patients' phenotype and metabolic defects incl. : - Reduced GOT2 protein levels (due to lower expression/impaired stability) and diminished activity in patient fibroblasts (lower activity was also shown for carriers). Rescue of the GOT enzymatic activity was observed upon transduction of patient fibroblasts using lentiviral particles with wt GOT2. - Impairment of de novo serine biosynthesis in patient (and to a lesser extent in carrier) fibroblasts compared to controls. This was similar in GOT2-knockout HEK293 cells. Serine biosynthesis in these cells was restored by pyruvate supplementation. - CRISPR/Cas9 Got2-knockout mice resulted in early lethality (during pregnancy). Heterozygous mice were viable and healthy. - Morpholino knockdown of got2a in zebrafish was shown to perturb embryonic development (smaller head, slow circulation, bend body, brain developmental defects, etc). Pyridoxine and serine in embryo water resulted in milder phenotypes/improved morphant survival. Zebrafish got2a morphants had seizure-like spikes upon EEG that were rescued by treatment with pyridoxine. GOT2 is not associated with any phenotype in OMIM/G2P. As a result, this gene can be considered for inclusion in both epilepsy and ID gene panels probably as green (3 families, relevant phenotypes and severity, evidence from cell and animal studies) or amber. [Please consider inclusion in other relevant panels eg. mitochondrial disorders, metabolic disorders and/or addition of the 'treatable' tag]. Sources: Literature
25 Aug 2019	Early onset or syndromic epilepsy v1.256	TRAPPC6B	Konstantinos Varvagiannis reviewed gene: TRAPPC6B: Rating: AMBER; Mode of pathogenicity: None; Publications: 28626029, 28397838, DOI 10.1055/s-0039-1693664; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
25 Aug 2019	Early onset or syndromic epilepsy v1.256	KCNMA1	Konstantinos Varvagiannis reviewed gene: KCNMA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31427379, 31152168, 27567911; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
23 Aug 2019	Early onset or syndromic epilepsy v1.256	KCND2	Alison Callaway reviewed gene: KCND2: Rating: RED; Mode of pathogenicity: None; Publications: 16934482; Phenotypes: ; Mode of inheritance: None
23 Aug 2019	Early onset or syndromic epilepsy v1.256	CSNK2A1	Alison Callaway reviewed gene: CSNK2A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27048600; Phenotypes: Neurodevelopmental abnormalities and dysmorphic features; Mode of inheritance: None
23 Aug 2019	Early onset or syndromic epilepsy v1.256	ZNF142	Alison Callaway reviewed gene: ZNF142: Rating: AMBER; Mode of pathogenicity: None; Publications: 31036918; Phenotypes: NEURODEVELOPMENTAL DISORDER WITH IMPAIRED SPEECH AND HYPERKINETIC MOVEMENTS; Mode of inheritance: None
23 Aug 2019	Early onset or syndromic epilepsy v1.256	USP7	Alison Callaway reviewed gene: USP7: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
23 Aug 2019	Early onset or syndromic epilepsy v1.256	TRRAP	Alison Callaway reviewed gene: TRRAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 28628100, 30827496; Phenotypes: DEVELOPMENTAL DELAY WITH OR WITHOUT DYSMORPHIC FACIES AND AUTISM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
23 Aug 2019	Early onset or syndromic epilepsy v1.256	TRPM3	Alison Callaway reviewed gene: TRPM3: Rating: AMBER; Mode of pathogenicity: None; Publications: 29156220; Phenotypes: ; Mode of inheritance: None
23 Aug 2019	Early onset or syndromic epilepsy v1.256	CLCN6	Alison Callaway reviewed gene: CLCN6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
23 Aug 2019	Early onset or syndromic epilepsy v1.256	AIMP2	Alison Callaway reviewed gene: AIMP2: Rating: AMBER; Mode of pathogenicity: None; Publications: 26795593; Phenotypes: Epileptic Encephalopathy, Infantile Spasms; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
23 Aug 2019	Early onset or syndromic epilepsy v1.256	AFF3	Alison Callaway reviewed gene: AFF3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
23 Aug 2019	Early onset or syndromic epilepsy v1.256	ALPL	Alison Callaway changed review comment from: Epilepsy can be associated with hypophosphasia; no further literature identified. From reviews below, appears to have sufficient evidence for a green gene.; to: Epilepsy can be associated with hypophosphatasia; no further literature identified. From reviews below, appears to have sufficient evidence for a green gene.
23 Aug 2019	Early onset or syndromic epilepsy v1.256	ALPL	Alison Callaway reviewed gene: ALPL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
23 Aug 2019	Early onset or syndromic epilepsy v1.256	EMX2	Alison Callaway reviewed gene: EMX2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
23 Aug 2019	Early onset or syndromic epilepsy v1.256	NPRL2	Alison Callaway reviewed gene: NPRL2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
23 Aug 2019	Early onset or syndromic epilepsy v1.256	KCNMA1	Alison Callaway reviewed gene: KCNMA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29933521; Phenotypes: Generalised epilepsy and paroxysmal dyskinesia; Mode of inheritance: None
23 Aug 2019	Early onset or syndromic epilepsy v1.256	TUBB2A	Alison Callaway reviewed gene: TUBB2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 24702957; Phenotypes: CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
23 Aug 2019	Early onset or syndromic epilepsy v1.256	SLC25A12	Alison Callaway reviewed gene: SLC25A12: Rating: GREEN; Mode of pathogenicity: None; Publications: 19641205, 24515575, 27290639, 26633542; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
23 Aug 2019	Early onset or syndromic epilepsy v1.256	HCN2	Alison Callaway reviewed gene: HCN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29064616, 22131395; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
23 Aug 2019	Early onset or syndromic epilepsy v1.256	HCN2	Alison Callaway Deleted their review
23 Aug 2019	Early onset or syndromic epilepsy v1.256	HCN2	Alison Callaway reviewed gene: HCN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29064616, 22131395; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
20 Aug 2019	Early onset or syndromic epilepsy v1.256	SPATA5	Sarah Leigh Publications for gene: SPATA5 were set to PMID: 27246907; 29343804; 26299366
20 Aug 2019	Early onset or syndromic epilepsy v1.255	SPATA5	Sarah Leigh Classified gene: SPATA5 as Green List (high evidence)
20 Aug 2019	Early onset or syndromic epilepsy v1.255	SPATA5	Sarah Leigh Added comment: Comment on list classification: Based on review from Rachel Jones (GSTT): Tanaka et al PMID: 26299366 identified "14 individuals [from 10 families] with microcephaly, developmental delay, intellectual disability, hypotonia, spasticity, seizures, sensorineural hearing loss, cortical visual impairment, and rare autosomal-recessive predicted pathogenic variants" in SPATA5 Puussep et al PMID: 29343804 describes 5 further patients "with psychomotor developmental delay, microcephaly, epilepsy and hearing impairment, who were thought clinically to have a mitochondrial disease with subsequent whole-exome sequencing analysis detecting compound heterozygous variants in the SPATA5 gene" Szczaluba et al PMID: 28293831 describes a family where a sibling has isolated sensorineural hearing loss and the same two pathogenic SPATA5 variants as her more typically affected sister. In addition, typically affected individuals may present as congenital SNHL on newborn hearing screen prior to onset of seizures, microcephaly and intellectual disability.
20 Aug 2019	Early onset or syndromic epilepsy v1.255	SPATA5	Sarah Leigh Gene: spata5 has been classified as Green List (High Evidence).
19 Aug 2019	Early onset or syndromic epilepsy v1.254	SPATA5	Rachel Jones gene: SPATA5 was added gene: SPATA5 was added to Genetic epilepsy syndromes. Sources: Other Mode of inheritance for gene: SPATA5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPATA5 were set to PMID: 27246907; 29343804; 26299366 Phenotypes for gene: SPATA5 were set to Epilepsy, hearing loss, and mental retardation syndrome 616577 Penetrance for gene: SPATA5 were set to Incomplete Review for gene: SPATA5 was set to GREEN Added comment: Greater than 15 families have been identified in multiple publications showing that patients with SPATA5 biallelic variants present with intellectual disability, epilepsy, microcephaly and hearing loss. May present as epileptic encephalopathy/epilepsy in the first year of life prior to onset of obvious developmental delay. Sources: Other
19 Aug 2019	Early onset or syndromic epilepsy v1.254	SLC2A1	Ellen McDonagh edited their review of gene: SLC2A1: Added comment: Added the tag 'treatable' as a ketogenic diet can help ameloriate symptoms (PMID: 29303961).; Changed publications: 29303961
19 Aug 2019	Early onset or syndromic epilepsy v1.254	SLC2A1	Ellen McDonagh Tag treatable tag was added to gene: SLC2A1.
19 Aug 2019	Early onset or syndromic epilepsy v1.254	KMT2E	Louise Daugherty Added comment: Comment on phenotypes: added OMIM MIM id
19 Aug 2019	Early onset or syndromic epilepsy v1.254	KMT2E	Louise Daugherty Phenotypes for gene: KMT2E were changed from Global developmental delay; Intellectual disability; Autism; Seizures; Abnormality of skull size to O'Donnell-Luria-Rodan syndrome, 618512; Global developmental delay; Intellectual disability; Autism; Seizures; Abnormality of skull size
19 Aug 2019	Early onset or syndromic epilepsy v1.253	CACNA1B	Louise Daugherty Added comment: Comment on phenotypes: added OMIM MIM id
19 Aug 2019	Early onset or syndromic epilepsy v1.253	CACNA1B	Louise Daugherty Phenotypes for gene: CACNA1B were changed from Global developmental delay; Developmental regression; Seizures; Intellectual disability; Abnormality of movement; Progressive Epilepsy-Dyskinesia to Neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements, 618497; Global developmental delay; Developmental regression; Seizures; Intellectual disability; Abnormality of movement; Progressive Epilepsy-Dyskinesia
15 Aug 2019	Early onset or syndromic epilepsy v1.252	ISCA-46290-Gain	Rebecca Foulger Haploinsufficiency Score for ISCA-46290-Gain was changed from to None. Source NHS GMS was added to Region: ISCA-46290-Gain.
15 Aug 2019	Early onset or syndromic epilepsy v1.251	ISCA-37493-Loss	Rebecca Foulger Triplosensitivity Score for ISCA-37493-Loss was changed from to None. Source NHS GMS was added to Region: ISCA-37493-Loss.
15 Aug 2019	Early onset or syndromic epilepsy v1.250	ISCA-37478-Loss	Rebecca Foulger Triplosensitivity Score for ISCA-37478-Loss was changed from to None. Source NHS GMS was added to Region: ISCA-37478-Loss.
15 Aug 2019	Early onset or syndromic epilepsy v1.249	ISCA-37478-Gain	Rebecca Foulger Haploinsufficiency Score for ISCA-37478-Gain was changed from to None. Source NHS GMS was added to Region: ISCA-37478-Gain.
15 Aug 2019	Early onset or syndromic epilepsy v1.248	ISCA-37434-Loss	Rebecca Foulger Triplosensitivity Score for ISCA-37434-Loss was changed from to None. Source NHS GMS was added to Region: ISCA-37434-Loss.
15 Aug 2019	Early onset or syndromic epilepsy v1.247	ISCA-37432-Gain	Rebecca Foulger Haploinsufficiency Score for ISCA-37432-Gain was changed from to None. Source NHS GMS was added to Region: ISCA-37432-Gain.
15 Aug 2019	Early onset or syndromic epilepsy v1.246	ISCA-37430-Loss	Rebecca Foulger Triplosensitivity Score for ISCA-37430-Loss was changed from to None. Source NHS GMS was added to Region: ISCA-37430-Loss.
15 Aug 2019	Early onset or syndromic epilepsy v1.245	ISCA-37429-Loss	Rebecca Foulger Triplosensitivity Score for ISCA-37429-Loss was changed from to None. Source NHS GMS was added to Region: ISCA-37429-Loss.
15 Aug 2019	Early onset or syndromic epilepsy v1.244	ISCA-37423-Gain	Rebecca Foulger Haploinsufficiency Score for ISCA-37423-Gain was changed from to None. Source NHS GMS was added to Region: ISCA-37423-Gain.
15 Aug 2019	Early onset or syndromic epilepsy v1.243	ISCA-37415-Loss	Rebecca Foulger Triplosensitivity Score for ISCA-37415-Loss was changed from to None. Source NHS GMS was added to Region: ISCA-37415-Loss.
15 Aug 2019	Early onset or syndromic epilepsy v1.242	ISCA-37411-Loss	Rebecca Foulger Triplosensitivity Score for ISCA-37411-Loss was changed from to None. Source NHS GMS was added to Region: ISCA-37411-Loss.
15 Aug 2019	Early onset or syndromic epilepsy v1.241	ISCA-37404-Loss	Rebecca Foulger Triplosensitivity Score for ISCA-37404-Loss was changed from to None. Source NHS GMS was added to Region: ISCA-37404-Loss.
15 Aug 2019	Early onset or syndromic epilepsy v1.240	ISCA-46295-Loss	Rebecca Foulger Triplosensitivity Score for ISCA-46295-Loss was changed from to None. Source NHS GMS was added to Region: ISCA-46295-Loss.
15 Aug 2019	Early onset or syndromic epilepsy v1.239	ISCA-46295-Loss	Rebecca Foulger commented on Region: ISCA-46295-Loss
15 Aug 2019	Early onset or syndromic epilepsy v1.239	ISCA-46290-Gain	Rebecca Foulger commented on Region: ISCA-46290-Gain
15 Aug 2019	Early onset or syndromic epilepsy v1.239	ISCA-37493-Loss	Rebecca Foulger reviewed Region: ISCA-37493-Loss: Rating: ; Mode of pathogenicity: None; Publications: 28283832; Phenotypes: ; Mode of inheritance: None
15 Aug 2019	Early onset or syndromic epilepsy v1.239	ISCA-37478-Loss	Rebecca Foulger commented on Region: ISCA-37478-Loss
15 Aug 2019	Early onset or syndromic epilepsy v1.239	ISCA-37478-Gain	Rebecca Foulger commented on Region: ISCA-37478-Gain
15 Aug 2019	Early onset or syndromic epilepsy v1.239	ISCA-37434-Loss	Rebecca Foulger commented on Region: ISCA-37434-Loss
15 Aug 2019	Early onset or syndromic epilepsy v1.239	ISCA-37432-Gain	Rebecca Foulger commented on Region: ISCA-37432-Gain
15 Aug 2019	Early onset or syndromic epilepsy v1.239	ISCA-37430-Loss	Rebecca Foulger commented on Region: ISCA-37430-Loss
15 Aug 2019	Early onset or syndromic epilepsy v1.239	ISCA-37429-Loss	Rebecca Foulger commented on Region: ISCA-37429-Loss
15 Aug 2019	Early onset or syndromic epilepsy v1.239	ISCA-37415-Loss	Rebecca Foulger reviewed Region: ISCA-37415-Loss: Rating: ; Mode of pathogenicity: None; Publications: 10573006; Phenotypes: ; Mode of inheritance: None
15 Aug 2019	Early onset or syndromic epilepsy v1.239	ISCA-37423-Gain	Rebecca Foulger reviewed Region: ISCA-37423-Gain: Rating: ; Mode of pathogenicity: None; Publications: 28533195; Phenotypes: ; Mode of inheritance: None
15 Aug 2019	Early onset or syndromic epilepsy v1.239	ISCA-37411-Loss	Rebecca Foulger reviewed Region: ISCA-37411-Loss: Rating: ; Mode of pathogenicity: None; Publications: 19289393; Phenotypes: ; Mode of inheritance: None
15 Aug 2019	Early onset or syndromic epilepsy v1.239	ISCA-37404-Loss	Rebecca Foulger commented on Region: ISCA-37404-Loss
15 Aug 2019	Early onset or syndromic epilepsy v1.239	GATM	Rebecca Foulger Phenotypes for gene: GATM were changed from to Cerebral creatine deficiency syndrome 3, 612718
15 Aug 2019	Early onset or syndromic epilepsy v1.238	GATM	Rebecca Foulger Mode of inheritance for gene: GATM was changed from to BIALLELIC, autosomal or pseudoautosomal
15 Aug 2019	Early onset or syndromic epilepsy v1.237	GATM	Rebecca Foulger Publications for gene: GATM were set to
15 Aug 2019	Early onset or syndromic epilepsy v1.236	SETD5	Rebecca Foulger changed review comment from: Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. Although four reviewers agreed it should be on EE panel, there is limited evidence of a seizure phenotype. PMID:26482601: (Kobayashi et al., 2016) examined 11 patients with early-onset epileptic encephalopathy, and SETD5 variants were amongst the findings. Therefore awaited clinical input on whether SETD5 should be demoted on this panel.; to: Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. In summary: although four reviewers agreed it should be on EE panel, there is limited evidence of a seizure phenotype. PMID:26482601: (Kobayashi et al., 2016) examined 11 patients with early-onset epileptic encephalopathy, and SETD5 variants were amongst the findings. Therefore consider demoting SETD5.
15 Aug 2019	Early onset or syndromic epilepsy v1.236	LYST	Rebecca Foulger changed review comment from: Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. Although the mouse model displays seizures (PMID:16518687), there is limited evidence of patients with seizures (no mention of seizures in PMID:9215679, and one 1990 report of Chédiak-Higashi syndrome with seizures from PMID:10450360). Therefore awaiting clinical opinion on whether LYST should be demoted on this panel.; to: Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. In summary: although the mouse model displays seizures (PMID:16518687), there is limited evidence of patients with seizures (no mention of seizures in PMID:9215679, and one 1990 report of Chédiak-Higashi syndrome with seizures from PMID:10450360). Therefore consider demoting LYST.
15 Aug 2019	Early onset or syndromic epilepsy v1.236	KIF1BP	Rebecca Foulger changed review comment from: Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. Although the association with GOLDBERG-SHPRINTZEN MEGACOLON SYNDROME is strong, there is little direct evidence for seizures (PMID:28277559 identifies one case). Therefore awaiting clinical opinion on whether KIF1BP should be demoted.; to: Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. In summary: although the association with GOLDBERG-SHPRINTZEN MEGACOLON SYNDROME is strong, there is little direct evidence for seizures (PMID:28277559 identifies one case). Therefore consider demoting KIF1BP.
15 Aug 2019	Early onset or syndromic epilepsy v1.236	AKT1	Rebecca Foulger Marked gene: AKT1 as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.236	AKT1	Rebecca Foulger Gene: akt1 has been classified as Red List (Low Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.236	PTEN	Rebecca Foulger Marked gene: PTEN as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.236	PTEN	Rebecca Foulger Gene: pten has been classified as Red List (Low Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.236	PIK3CA	Rebecca Foulger Marked gene: PIK3CA as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.236	PIK3CA	Rebecca Foulger Gene: pik3ca has been classified as Red List (Low Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.236	PIK3CA	Rebecca Foulger Classified gene: PIK3CA as Red List (low evidence)
15 Aug 2019	Early onset or syndromic epilepsy v1.236	PIK3CA	Rebecca Foulger Gene: pik3ca has been classified as Red List (Low Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.235	PIK3CA	Rebecca Foulger commented on gene: PIK3CA: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed to demote PIK3CA from Green to Red. This panel is not the appropriate test for somatic variant detection due to the coverage. R110 Segmental overgrowth disorders (panel #98) should be used where megalencephaly is present to allow detection of somatic mosaic mutations.
15 Aug 2019	Early onset or syndromic epilepsy v1.235	PTEN	Rebecca Foulger commented on gene: PTEN: Added tags: 'mosaicism' and 'somatic'.
15 Aug 2019	Early onset or syndromic epilepsy v1.235	PTEN	Rebecca Foulger Classified gene: PTEN as Red List (low evidence)
15 Aug 2019	Early onset or syndromic epilepsy v1.235	PTEN	Rebecca Foulger Gene: pten has been classified as Red List (Low Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.234	PTEN	Rebecca Foulger commented on gene: PTEN: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed to demote AKT1 from Green to Red. This panel is not the appropriate test for somatic variant detection due to the coverage. R110 Segmental overgrowth disorders (panel #98) should be used where megalencephaly is present to allow detection of somatic mosaic mutations.
15 Aug 2019	Early onset or syndromic epilepsy v1.234	PTEN	Rebecca Foulger Tag mosaicism tag was added to gene: PTEN. Tag somatic tag was added to gene: PTEN.
15 Aug 2019	Early onset or syndromic epilepsy v1.234	AKT1	Rebecca Foulger Classified gene: AKT1 as Red List (low evidence)
15 Aug 2019	Early onset or syndromic epilepsy v1.234	AKT1	Rebecca Foulger Gene: akt1 has been classified as Red List (Low Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.233	AKT1	Rebecca Foulger commented on gene: AKT1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed to demote AKT1 from Green to Red. This panel is not the appropriate test for somatic variant detection due to the coverage. R110 Segmental overgrowth disorders (panel #98) should be used where megalencephaly is present to allow detection of somatic mosaic mutations.
15 Aug 2019	Early onset or syndromic epilepsy v1.233	WDR37	Rebecca Foulger Marked gene: WDR37 as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.233	WDR37	Rebecca Foulger Gene: wdr37 has been classified as Green List (High Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.233	PEX5	Rebecca Foulger Marked gene: PEX5 as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.233	PEX5	Rebecca Foulger Gene: pex5 has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.233	KIAA1109	Rebecca Foulger Marked gene: KIAA1109 as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.233	KIAA1109	Rebecca Foulger Gene: kiaa1109 has been classified as Green List (High Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.233	GTPBP3	Rebecca Foulger Marked gene: GTPBP3 as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.233	GTPBP3	Rebecca Foulger Gene: gtpbp3 has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.233	EIF2B3	Rebecca Foulger Marked gene: EIF2B3 as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.233	EIF2B3	Rebecca Foulger Gene: eif2b3 has been classified as Green List (High Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.233	EIF2B1	Rebecca Foulger Marked gene: EIF2B1 as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.233	EIF2B1	Rebecca Foulger Gene: eif2b1 has been classified as Green List (High Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.233	EFHC1	Rebecca Foulger Marked gene: EFHC1 as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.233	EFHC1	Rebecca Foulger Gene: efhc1 has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.233	DPM2	Rebecca Foulger Marked gene: DPM2 as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.233	DPM2	Rebecca Foulger Gene: dpm2 has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.233	CUL4B	Rebecca Foulger Marked gene: CUL4B as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.233	CUL4B	Rebecca Foulger Gene: cul4b has been classified as Green List (High Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.233	CNPY3	Rebecca Foulger Marked gene: CNPY3 as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.233	CNPY3	Rebecca Foulger Gene: cnpy3 has been classified as Green List (High Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.233	PTS	Rebecca Foulger Marked gene: PTS as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.233	PTS	Rebecca Foulger Gene: pts has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.233	PTS	Rebecca Foulger Classified gene: PTS as Amber List (moderate evidence)
15 Aug 2019	Early onset or syndromic epilepsy v1.233	PTS	Rebecca Foulger Gene: pts has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.232	PTS	Rebecca Foulger commented on gene: PTS: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene should be rated Amber to match the rating on the 'Inborn errors of metabolism' panel. The prevailing phenotype is a movement disorder. Demoted from Green to Amber.
15 Aug 2019	Early onset or syndromic epilepsy v1.232	PTS	Rebecca Foulger commented on gene: PTS: Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. In summary: Severe Hyperphenylalaninemia, BH4-deficient, is accepted to include seizures (PMID:8801112). Because this condition is diagnosed and treated from an early age, seizures may not be reported frequently. PMID:31000854 (Ahmed et al., 2019)assessed hyperphenylalaninemia patients and found 14/18 (78%) had seizures and ID however genetic analysis to see which of these had PTPS/PTS variants was not performed. PMID:9222757 report 1 case of seizures.
15 Aug 2019	Early onset or syndromic epilepsy v1.232	KCNA1	Rebecca Foulger Marked gene: KCNA1 as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.232	KCNA1	Rebecca Foulger Gene: kcna1 has been classified as Green List (High Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.232	KCNA1	Rebecca Foulger commented on gene: KCNA1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is sufficient evidence to rate this gene Green. Kept rating as Green.
15 Aug 2019	Early onset or syndromic epilepsy v1.232	WDR62	Rebecca Foulger Marked gene: WDR62 as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.232	WDR62	Rebecca Foulger Gene: wdr62 has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.232	WDR62	Rebecca Foulger Classified gene: WDR62 as Amber List (moderate evidence)
15 Aug 2019	Early onset or syndromic epilepsy v1.232	WDR62	Rebecca Foulger Gene: wdr62 has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.231	WDR62	Rebecca Foulger commented on gene: WDR62: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene should be rated Amber- the microcephaly panels are more appropriate for testing. Demoted from Green to Amber.
15 Aug 2019	Early onset or syndromic epilepsy v1.231	TSEN2	Rebecca Foulger Marked gene: TSEN2 as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.231	TSEN2	Rebecca Foulger Gene: tsen2 has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.231	TSEN2	Rebecca Foulger Classified gene: TSEN2 as Amber List (moderate evidence)
15 Aug 2019	Early onset or syndromic epilepsy v1.231	TSEN2	Rebecca Foulger Gene: tsen2 has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.230	TSEN2	Rebecca Foulger commented on gene: TSEN2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene should be rated Amber because epilepsy is unlikely to be the primary presenting feature. Demoted from Green to Amber.
15 Aug 2019	Early onset or syndromic epilepsy v1.230	SCN9A	Rebecca Foulger Marked gene: SCN9A as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.230	SCN9A	Rebecca Foulger Gene: scn9a has been classified as Green List (High Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.230	SCN9A	Rebecca Foulger commented on gene: SCN9A: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is sufficient evidence to rate this gene Green. Kept rating as Green.
15 Aug 2019	Early onset or syndromic epilepsy v1.230	FLNA	Rebecca Foulger Marked gene: FLNA as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.230	FLNA	Rebecca Foulger Gene: flna has been classified as Green List (High Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.230	FLNA	Rebecca Foulger commented on gene: FLNA: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is sufficient evidence to rate this gene Green. Kept rating as Green.
15 Aug 2019	Early onset or syndromic epilepsy v1.230	FGFR3	Rebecca Foulger Classified gene: FGFR3 as Amber List (moderate evidence)
15 Aug 2019	Early onset or syndromic epilepsy v1.230	FGFR3	Rebecca Foulger Gene: fgfr3 has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.229	FGFR3	Rebecca Foulger Marked gene: FGFR3 as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.229	FGFR3	Rebecca Foulger Gene: fgfr3 has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.229	FGFR3	Rebecca Foulger Classified gene: FGFR3 as Amber List (moderate evidence)
15 Aug 2019	Early onset or syndromic epilepsy v1.229	FGFR3	Rebecca Foulger Gene: fgfr3 has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.228	FGFR3	Rebecca Foulger commented on gene: FGFR3: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene should be rated Amber because the Craniosynostosis panel is more appropriate for testing. Demoted from Green to Amber.
15 Aug 2019	Early onset or syndromic epilepsy v1.228	ATP1A2	Rebecca Foulger Marked gene: ATP1A2 as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.228	ATP1A2	Rebecca Foulger Gene: atp1a2 has been classified as Green List (High Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.228	ATP1A2	Rebecca Foulger commented on gene: ATP1A2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is sufficient evidence to rate this gene Green. Kept rating as Green.
15 Aug 2019	Early onset or syndromic epilepsy v1.228	LYST	Rebecca Foulger Marked gene: LYST as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.228	LYST	Rebecca Foulger Gene: lyst has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.228	SETD5	Rebecca Foulger Marked gene: SETD5 as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.228	SETD5	Rebecca Foulger Gene: setd5 has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.228	WDR45B	Rebecca Foulger Marked gene: WDR45B as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.228	WDR45B	Rebecca Foulger Gene: wdr45b has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.228	WDR45B	Rebecca Foulger Classified gene: WDR45B as Amber List (moderate evidence)
15 Aug 2019	Early onset or syndromic epilepsy v1.228	WDR45B	Rebecca Foulger Gene: wdr45b has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.227	WDR45B	Rebecca Foulger commented on gene: WDR45B: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green, and an Amber rating is appropriate. Demoted from Green to Amber.
15 Aug 2019	Early onset or syndromic epilepsy v1.227	WDR45B	Rebecca Foulger commented on gene: WDR45B: Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. In summary, the evidence is borderline: PMID:28503735 (Suleiman et al) report 6 individuals from 3 families with homozygous pathogenic variants in WDR45B, and 2 of the families (5 indivs) had seizures- seizures were not reported in the sole individual from family 3.
15 Aug 2019	Early onset or syndromic epilepsy v1.227	SETD5	Rebecca Foulger Classified gene: SETD5 as Amber List (moderate evidence)
15 Aug 2019	Early onset or syndromic epilepsy v1.227	SETD5	Rebecca Foulger Gene: setd5 has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.226	SETD5	Rebecca Foulger commented on gene: SETD5: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green, and an Amber rating is appropriate. Demoted from Green to Amber.
15 Aug 2019	Early onset or syndromic epilepsy v1.226	SETD5	Rebecca Foulger commented on gene: SETD5: Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. Although four reviewers agreed it should be on EE panel, there is limited evidence of a seizure phenotype. PMID:26482601: (Kobayashi et al., 2016) examined 11 patients with early-onset epileptic encephalopathy, and SETD5 variants were amongst the findings. Therefore awaited clinical input on whether SETD5 should be demoted on this panel.
15 Aug 2019	Early onset or syndromic epilepsy v1.226	LYST	Rebecca Foulger Classified gene: LYST as Amber List (moderate evidence)
15 Aug 2019	Early onset or syndromic epilepsy v1.226	LYST	Rebecca Foulger Gene: lyst has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.225	LYST	Rebecca Foulger commented on gene: LYST: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green, and an Amber rating is appropriate. Demoted from Green to Amber.
15 Aug 2019	Early onset or syndromic epilepsy v1.225	LYST	Rebecca Foulger commented on gene: LYST: Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. Although the mouse model displays seizures (PMID:16518687), there is limited evidence of patients with seizures (no mention of seizures in PMID:9215679, and one 1990 report of Chédiak-Higashi syndrome with seizures from PMID:10450360). Therefore awaiting clinical opinion on whether LYST should be demoted on this panel.
15 Aug 2019	Early onset or syndromic epilepsy v1.225	KIF1BP	Rebecca Foulger Marked gene: KIF1BP as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.225	KIF1BP	Rebecca Foulger Gene: kif1bp has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.225	KIF1BP	Rebecca Foulger Classified gene: KIF1BP as Amber List (moderate evidence)
15 Aug 2019	Early onset or syndromic epilepsy v1.225	KIF1BP	Rebecca Foulger Gene: kif1bp has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.224	KIF1BP	Rebecca Foulger commented on gene: KIF1BP: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green, and an Amber rating is appropriate. Demoted from Green to Amber.
15 Aug 2019	Early onset or syndromic epilepsy v1.224	KIF1BP	Rebecca Foulger commented on gene: KIF1BP: Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. Although the association with GOLDBERG-SHPRINTZEN MEGACOLON SYNDROME is strong, there is little direct evidence for seizures (PMID:28277559 identifies one case). Therefore awaiting clinical opinion on whether KIF1BP should be demoted.
15 Aug 2019	Early onset or syndromic epilepsy v1.224	GRIA2	Rebecca Foulger changed review comment from: PMID:8938126 (animal model): GluR2 heterozygous (+/−) mice showed reduced motor coordination but no sign of seizure activity as measured by observation, EEG, or post-mortem analysis.; to: PMID:8938126- animal model doesn't report seizures: GluR2 heterozygous (+/−) mice showed reduced motor coordination but no sign of seizure activity as measured by observation, EEG, or post-mortem analysis.
15 Aug 2019	Early onset or syndromic epilepsy v1.224	WDR37	Rebecca Foulger Classified gene: WDR37 as Green List (high evidence)
15 Aug 2019	Early onset or syndromic epilepsy v1.224	WDR37	Rebecca Foulger Gene: wdr37 has been classified as Green List (High Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.223	WDR37	Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Promoted from Grey to Green.
15 Aug 2019	Early onset or syndromic epilepsy v1.223	WDR37	Rebecca Foulger commented on gene: WDR37: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green.
15 Aug 2019	Early onset or syndromic epilepsy v1.223	WDR37	Rebecca Foulger commented on gene: WDR37: WDR37 was added to the panel and rated Green by Konstantinos Varvagiannis. Although WDR37 is not yet associated with a disorder in OMIM or Gene2Phenotype, (as Konstantinos notes) there are sufficient unrelated cases from PMID:31327510 and PMID:31327508 with seizures (all 9 patients) for inclusion on the panel.
15 Aug 2019	Early onset or syndromic epilepsy v1.223	WDR37	Rebecca Foulger changed review comment from: Added missense tag: only missense variants reported so far (PMID:31327510).; to: Added missense tag: only missense variants reported so far (PMIDs 31327510, 31327508).
15 Aug 2019	Early onset or syndromic epilepsy v1.223	WDR37	Rebecca Foulger commented on gene: WDR37
15 Aug 2019	Early onset or syndromic epilepsy v1.223	WDR37	Rebecca Foulger Tag missense tag was added to gene: WDR37.
15 Aug 2019	Early onset or syndromic epilepsy v1.223	PIGU	Rebecca Foulger Marked gene: PIGU as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.223	PIGU	Rebecca Foulger Gene: pigu has been classified as Green List (High Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.223	PIGH	Rebecca Foulger Marked gene: PIGH as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.223	PIGH	Rebecca Foulger Gene: pigh has been classified as Green List (High Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.223	PIGC	Rebecca Foulger Marked gene: PIGC as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.223	PIGC	Rebecca Foulger Gene: pigc has been classified as Green List (High Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.223	RRM2B	Rebecca Foulger Marked gene: RRM2B as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.223	RRM2B	Rebecca Foulger Gene: rrm2b has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.223	TRAF7	Rebecca Foulger Marked gene: TRAF7 as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.223	TRAF7	Rebecca Foulger Gene: traf7 has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.223	TRAPPC12	Rebecca Foulger Marked gene: TRAPPC12 as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.223	TRAPPC12	Rebecca Foulger Gene: trappc12 has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.223	TRAPPC6B	Rebecca Foulger Marked gene: TRAPPC6B as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.223	TRAPPC6B	Rebecca Foulger Gene: trappc6b has been classified as Amber List (Moderate Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.223	GNB5	Rebecca Foulger Marked gene: GNB5 as ready
15 Aug 2019	Early onset or syndromic epilepsy v1.223	GNB5	Rebecca Foulger Gene: gnb5 has been classified as Green List (High Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.223	GNB5	Rebecca Foulger commented on gene: GNB5: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green.
15 Aug 2019	Early onset or syndromic epilepsy v1.223	TRAPPC6B	Rebecca Foulger commented on gene: TRAPPC6B: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene can remain as Amber.
15 Aug 2019	Early onset or syndromic epilepsy v1.223	TRAPPC12	Rebecca Foulger commented on gene: TRAPPC12: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene can remain as Amber:
15 Aug 2019	Early onset or syndromic epilepsy v1.223	TRAF7	Rebecca Foulger commented on gene: TRAF7: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene can remain as Amber: TRAF7 is Green on the Intellectual disability and Paediatric disorders panels, which would be appropriate for the presenting phenotype.
15 Aug 2019	Early onset or syndromic epilepsy v1.223	RRM2B	Rebecca Foulger commented on gene: RRM2B: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene can remain as Amber: RRM2B is Green on the 'Inborn errors of metabolism' panel (467) so will be Green on the Epilepsy Super panel (489).
15 Aug 2019	Early onset or syndromic epilepsy v1.223	PIGU	Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green: PIGx genes act in the same biochemical pathway. Promoted from Grey to Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green: PIGx genes act in the same biochemical pathway. Promoted from Grey to Green.
15 Aug 2019	Early onset or syndromic epilepsy v1.223	PIGH	Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green: PIGx genes act in the same biochemical pathway. Promoted from Amber to Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green: PIGx genes act in the same biochemical pathway. Promoted from Amber to Green.
15 Aug 2019	Early onset or syndromic epilepsy v1.223	PIGC	Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green: PIGx genes act in the same biochemical pathway. Promoted from Amber to Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green: PIGx genes act in the same biochemical pathway. Promoted from Amber to Green.
15 Aug 2019	Early onset or syndromic epilepsy v1.223	PEX5	Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that this gene can remain as Amber: PEX5 is Green on the 'Inborn errors of metabolism' panel (467) so will be Green on the Epilepsy Super panel (489).; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene can remain as Amber: PEX5 is Green on the 'Inborn errors of metabolism' panel (467) so will be Green on the Epilepsy Super panel (489).
15 Aug 2019	Early onset or syndromic epilepsy v1.223	KIAA1109	Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green- although epilepsy may be secondary to the cerebral malformations presentation, include KIAA1109 so that cases recruited through different routes are not missed. Promoted from Amber to Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green- although epilepsy may be secondary to the cerebral malformations presentation, include KIAA1109 so that cases recruited through different routes are not missed. Promoted from Amber to Green.
15 Aug 2019	Early onset or syndromic epilepsy v1.223	EIF2B3	Rebecca Foulger Classified gene: EIF2B3 as Green List (high evidence)
15 Aug 2019	Early onset or syndromic epilepsy v1.223	EIF2B3	Rebecca Foulger Gene: eif2b3 has been classified as Green List (High Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.222	EIF2B3	Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green. Epilepsy is a feature of Vanishing White Matter Disorder, and therefore should include on the panel for early diagnosis in children. Promoted from Amber to Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Epilepsy is a feature of Vanishing White Matter Disorder, and therefore should include on the panel for early diagnosis in children. Promoted from Amber to Green.
15 Aug 2019	Early onset or syndromic epilepsy v1.222	EIF2B1	Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green. Epilepsy is a feature of Vanishing White Matter Disorder, and therefore should include on the panel for early diagnosis in children. Promoted from Amber to Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Epilepsy is a feature of Vanishing White Matter Disorder, and therefore should include on the panel for early diagnosis in children. Promoted from Amber to Green.
15 Aug 2019	Early onset or syndromic epilepsy v1.222	EFHC1	Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that this gene should remain as Amber: EFHC1 may be a susceptibility locus. Currently insufficient evidence to support a monogenic association with epilepsy.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene should remain as Amber: EFHC1 may be a susceptibility locus. Currently insufficient evidence to support a monogenic association with epilepsy.
15 Aug 2019	Early onset or syndromic epilepsy v1.222	DPM2	Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that this gene can remain as Amber: DPM2 is Green on the 'Inborn errors of metabolism' panel (467) so will be Green on the Epilepsy Super panel (489).; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene can remain as Amber: DPM2 is Green on the 'Inborn errors of metabolism' panel (467) so will be Green on the Epilepsy Super panel (489).
15 Aug 2019	Early onset or syndromic epilepsy v1.222	CUL4B	Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green. Promoted from Amber to Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Promoted from Amber to Green.
15 Aug 2019	Early onset or syndromic epilepsy v1.222	CNPY3	Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green. Helen Lord (Oxford Medical Genetics Laboratories) notes that there are two further 2019 paper supporting inclusion. Promoted from Amber to Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Helen Lord (Oxford Medical Genetics Laboratories) notes that there are two further 2019 paper supporting inclusion. Promoted from Amber to Green.
15 Aug 2019	Early onset or syndromic epilepsy v1.222	PIGU	Rebecca Foulger Phenotypes for gene: PIGU were changed from Global developmental delay; Intellectual disability; Seizures; Cerebral atrophy; Cerebellar hypoplasia; Scoliosis to myoclonic seizures; focal myoclonic seizures; Global developmental delay; Intellectual disability; Seizures; Cerebral atrophy; Cerebellar hypoplasia; Scoliosis
15 Aug 2019	Early onset or syndromic epilepsy v1.221	PIGU	Rebecca Foulger Classified gene: PIGU as Green List (high evidence)
15 Aug 2019	Early onset or syndromic epilepsy v1.221	PIGU	Rebecca Foulger Gene: pigu has been classified as Green List (High Evidence).
15 Aug 2019	Early onset or syndromic epilepsy v1.220	PIGU	Rebecca Foulger commented on gene: PIGU: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green: PIGx genes act in the same biochemical pathway. Promoted from Grey to Green.
15 Aug 2019	Early onset or syndromic epilepsy v1.220	PIGU	Rebecca Foulger changed review comment from: PMID:31353022 (Knaus et al. 2019) report two homozygous missense mutations (c.209T>A [p.Ile70Lys] and c.1149C>A [p.Asn383Lys]) in 5 individuals from 3 unrelated families. All individuals presented with global DD severe-to-profound ID, muscular hypotonia, seizures (myoclonic and focal myoclonic in all 5 probands), brain anomalies, scoliosis, and mild facial dysmorphism. Sequencing confirmed that all parents were healthy carriers. c.209T>A has not been observed in gnomAD while c.1149C>A has been observed only in the heterozygous state (7/277194).; to: PMID:31353022 (Knaus et al. 2019) report two homozygous missense mutations (c.209T>A [p.Ile70Lys] and c.1149C>A [p.Asn383Lys]) in 5 individuals from 3 unrelated families. All individuals presented with global DD severe-to-profound ID, muscular hypotonia, seizures (myoclonic/focal myoclonic in all 5 probands), brain anomalies, scoliosis, and mild facial dysmorphism. Sequencing confirmed that all parents were healthy carriers. c.209T>A has not been observed in gnomAD while c.1149C>A has been observed only in the heterozygous state (7/277194).
15 Aug 2019	Early onset or syndromic epilepsy v1.220	PIGU	Rebecca Foulger commented on gene: PIGU: PIGU is not yet associated with a disorder in OMIM or Gene2Phenotype.
15 Aug 2019	Early onset or syndromic epilepsy v1.220	PIGU	Rebecca Foulger commented on gene: PIGU: PMID:31353022 (Knaus et al. 2019) report two homozygous missense mutations (c.209T>A [p.Ile70Lys] and c.1149C>A [p.Asn383Lys]) in 5 individuals from 3 unrelated families. All individuals presented with global DD severe-to-profound ID, muscular hypotonia, seizures (myoclonic and focal myoclonic in all 5 probands), brain anomalies, scoliosis, and mild facial dysmorphism. Sequencing confirmed that all parents were healthy carriers. c.209T>A has not been observed in gnomAD while c.1149C>A has been observed only in the heterozygous state (7/277194).
13 Aug 2019	Early onset or syndromic epilepsy v1.220	PIGH	Rebecca Foulger Classified gene: PIGH as Green List (high evidence)
13 Aug 2019	Early onset or syndromic epilepsy v1.220	PIGH	Rebecca Foulger Gene: pigh has been classified as Green List (High Evidence).
13 Aug 2019	Early onset or syndromic epilepsy v1.219	PIGH	Rebecca Foulger commented on gene: PIGH: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green: PIGx genes act in the same biochemical pathway. Promoted from Amber to Green.
13 Aug 2019	Early onset or syndromic epilepsy v1.219	PIGC	Rebecca Foulger Classified gene: PIGC as Green List (high evidence)
13 Aug 2019	Early onset or syndromic epilepsy v1.219	PIGC	Rebecca Foulger Gene: pigc has been classified as Green List (High Evidence).
13 Aug 2019	Early onset or syndromic epilepsy v1.218	PIGC	Rebecca Foulger commented on gene: PIGC: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green: PIGx genes act in the same biochemical pathway. Promoted from Amber to Green.
13 Aug 2019	Early onset or syndromic epilepsy v1.218	PEX5	Rebecca Foulger commented on gene: PEX5: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that this gene can remain as Amber: PEX5 is Green on the 'Inborn errors of metabolism' panel (467) so will be Green on the Epilepsy Super panel (489).
13 Aug 2019	Early onset or syndromic epilepsy v1.218	KIAA1109	Rebecca Foulger Classified gene: KIAA1109 as Green List (high evidence)
13 Aug 2019	Early onset or syndromic epilepsy v1.218	KIAA1109	Rebecca Foulger Gene: kiaa1109 has been classified as Green List (High Evidence).
13 Aug 2019	Early onset or syndromic epilepsy v1.217	KIAA1109	Rebecca Foulger commented on gene: KIAA1109: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green- although epilepsy may be secondary to the cerebral malformations presentation, include KIAA1109 so that cases recruited through different routes are not missed. Promoted from Amber to Green.
13 Aug 2019	Early onset or syndromic epilepsy v1.217	GTPBP3	Rebecca Foulger commented on gene: GTPBP3: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that this gene can remain as Amber: GTPBP3 is Green on the 'Inborn errors of metabolism' panel (467) so will be Green on the Epilepsy Super panel (489).
13 Aug 2019	Early onset or syndromic epilepsy v1.217	EIF2B3	Rebecca Foulger Classified gene: EIF2B3 as Amber List (moderate evidence)
13 Aug 2019	Early onset or syndromic epilepsy v1.217	EIF2B3	Rebecca Foulger Gene: eif2b3 has been classified as Amber List (Moderate Evidence).
13 Aug 2019	Early onset or syndromic epilepsy v1.216	EIF2B3	Rebecca Foulger commented on gene: EIF2B3: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green. Epilepsy is a feature of Vanishing White Matter Disorder, and therefore should include on the panel for early diagnosis in children. Promoted from Amber to Green.
13 Aug 2019	Early onset or syndromic epilepsy v1.216	EIF2B1	Rebecca Foulger Classified gene: EIF2B1 as Green List (high evidence)
13 Aug 2019	Early onset or syndromic epilepsy v1.216	EIF2B1	Rebecca Foulger Gene: eif2b1 has been classified as Green List (High Evidence).
13 Aug 2019	Early onset or syndromic epilepsy v1.215	EIF2B1	Rebecca Foulger commented on gene: EIF2B1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green. Epilepsy is a feature of Vanishing White Matter Disorder, and therefore should include on the panel for early diagnosis in children. Promoted from Amber to Green.
13 Aug 2019	Early onset or syndromic epilepsy v1.215	EFHC1	Rebecca Foulger commented on gene: EFHC1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that this gene should remain as Amber: EFHC1 may be a susceptibility locus. Currently insufficient evidence to support a monogenic association with epilepsy.
13 Aug 2019	Early onset or syndromic epilepsy v1.215	DPM2	Rebecca Foulger commented on gene: DPM2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that this gene can remain as Amber: DPM2 is Green on the 'Inborn errors of metabolism' panel (467) so will be Green on the Epilepsy Super panel (489).
13 Aug 2019	Early onset or syndromic epilepsy v1.215	CUL4B	Rebecca Foulger Classified gene: CUL4B as Green List (high evidence)
13 Aug 2019	Early onset or syndromic epilepsy v1.215	CUL4B	Rebecca Foulger Gene: cul4b has been classified as Green List (High Evidence).
13 Aug 2019	Early onset or syndromic epilepsy v1.214	CUL4B	Rebecca Foulger commented on gene: CUL4B: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green. Promoted from Amber to Green.
13 Aug 2019	Early onset or syndromic epilepsy v1.214	CNPY3	Rebecca Foulger Classified gene: CNPY3 as Green List (high evidence)
13 Aug 2019	Early onset or syndromic epilepsy v1.214	CNPY3	Rebecca Foulger Gene: cnpy3 has been classified as Green List (High Evidence).
13 Aug 2019	Early onset or syndromic epilepsy v1.213	CNPY3	Rebecca Foulger commented on gene: CNPY3: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green. Helen Lord (Oxford Medical Genetics Laboratories) notes that there are two further 2019 paper supporting inclusion. Promoted from Amber to Green.
13 Aug 2019	Early onset or syndromic epilepsy v1.213	NPRL2	Rebecca Foulger commented on gene: NPRL2: NPRL2 re-reviewed for curation of GMS epilepsy panel: Sufficient cases for inclusion but variants in unaffected family members (explained by the authors as incomplete penetrance). Other members of the complex, NPRL3 and DEPDC5, are Green on the panel. Since the last curation there has been a Green review by Deb Pal (Kings College London): PMID:30093711 (2019) note 3 further probands with epilepsy (including 1 with infantile spasm and unclear effect on the protein). They also note incomplete penetrance for variants in their cohort of 73 patients (covering DEPDC5 + NPRL2 + NPRL3 genes which all form the GATOR1 complex together). Awaiting clinical review for final gene rating.
13 Aug 2019	Early onset or syndromic epilepsy v1.213	IKBKG	Rebecca Foulger Added comment: Comment on mode of inheritance: OMIM lists XLD inheritance for Incontinentia pigmenti (MIM:308300).
13 Aug 2019	Early onset or syndromic epilepsy v1.213	IKBKG	Rebecca Foulger Mode of inheritance for gene: IKBKG was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
13 Aug 2019	Early onset or syndromic epilepsy v1.212	ARHGEF9	Rebecca Foulger Added comment: Comment on mode of inheritance: OMIM lists XLR mode of inheritance for 'Epileptic encephalopathy, early infantile, 8' (MIM:300607). Gene2Phenotype lists hemizygous mode of inheritance (XLR) for EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 8.
13 Aug 2019	Early onset or syndromic epilepsy v1.212	ARHGEF9	Rebecca Foulger Mode of inheritance for gene: ARHGEF9 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
13 Aug 2019	Early onset or syndromic epilepsy v1.211	NDUFA1	Rebecca Foulger Added comment: Comment on mode of inheritance: There is a case of female with variant and symptoms in PMID:21596602. (Mayr et al., 2011), but she does not have epilepsy but rather a metabolic defect. Therefore XLD is appropriate for metabolism panel but MOI is kept as XLR on this epilepsy panel for now.
13 Aug 2019	Early onset or syndromic epilepsy v1.211	NDUFA1	Rebecca Foulger Mode of inheritance for gene: NDUFA1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
13 Aug 2019	Early onset or syndromic epilepsy v1.210	SLC16A2	Rebecca Foulger Added comment: Comment on mode of inheritance: MOI is recorded as hemizygous in Gene2Phenotype and XL in OMIM. XLR inheritance was confirmed with reviewer, as stated by Ellen McDonagh.
13 Aug 2019	Early onset or syndromic epilepsy v1.210	SLC16A2	Rebecca Foulger Mode of inheritance for gene: SLC16A2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
13 Aug 2019	Early onset or syndromic epilepsy v1.209	PIGA	Rebecca Foulger Added comment: Comment on mode of inheritance: OMIM records XLR inheritance for 'Multiple congenital anomalies-hypotonia-seizures syndrome 2 (MIM:300868). Gene2Phenotype reports 'hemizygous' allelic requirement for MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 2. Johnston et al., 2012 (PMID:22305531) report 3 deceased males and 2 carrier females. Both carrier females had 100% skewed X-inactivation and neither presented with a phenotype.
13 Aug 2019	Early onset or syndromic epilepsy v1.209	PIGA	Rebecca Foulger Mode of inheritance for gene: PIGA was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
13 Aug 2019	Early onset or syndromic epilepsy v1.208	MED12	Rebecca Foulger Added comment: Comment on mode of inheritance: Allelic requirement listed in Gene2Phenotype is 'hemizygous' for both 'OPITZ-KAVEGGIA SYNDROME' and 'LUJAN-FRYNS SYNDROME'.
13 Aug 2019	Early onset or syndromic epilepsy v1.208	MED12	Rebecca Foulger Mode of inheritance for gene: MED12 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
13 Aug 2019	Early onset or syndromic epilepsy v1.207	MAGI2	Rebecca Foulger Added comment: Comment on mode of inheritance: OMIM lists AR inheritance for 'Nephrotic syndrome, type 15' (MIM:617609). Gene2Phenotype lists 'monoallelic' inheritance for EARLY ONSET EPILEPTIC ENCEPHALOPATHY.
13 Aug 2019	Early onset or syndromic epilepsy v1.207	MAGI2	Rebecca Foulger Mode of inheritance for gene: MAGI2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
13 Aug 2019	Early onset or syndromic epilepsy v1.206	IDH2	Rebecca Foulger Added comment: Comment on mode of inheritance: The mode of inheritance for IDH2 is currently MONOALLELIC on the 'Intellectual disability' panel, and the 'Inborn errors of metabolism' panel.
13 Aug 2019	Early onset or syndromic epilepsy v1.206	IDH2	Rebecca Foulger Mode of inheritance for gene: IDH2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
13 Aug 2019	Early onset or syndromic epilepsy v1.205	IDH2	Rebecca Foulger Phenotypes for gene: IDH2 were changed from D-2-hydroxyglutaric aciduria 2 to D-2-hydroxyglutaric aciduria 2, 613657
13 Aug 2019	Early onset or syndromic epilepsy v1.204	IDH2	Rebecca Foulger Publications for gene: IDH2 were set to
13 Aug 2019	Early onset or syndromic epilepsy v1.203	NRXN1	Rebecca Foulger Added comment: Comment on mode of inheritance: PMID:30031152 (Al Shehhi et al.) report heterozygous deletions of NRXN1 with phenotypes including seizures. At least PMID:21964664 (Harrison et al.) and PMID:19896112 report a biallelic mode of inheritance.
13 Aug 2019	Early onset or syndromic epilepsy v1.203	NRXN1	Rebecca Foulger Mode of inheritance for gene: NRXN1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
13 Aug 2019	Early onset or syndromic epilepsy v1.202	SLC35A2	Rebecca Foulger Added comment: Comment on mode of inheritance: MOI in OMIM for SLC35A2 is listed as X-linked dominant.
13 Aug 2019	Early onset or syndromic epilepsy v1.202	SLC35A2	Rebecca Foulger Mode of inheritance for gene: SLC35A2 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
13 Aug 2019	Early onset or syndromic epilepsy v1.201	KCNJ11	Rebecca Foulger changed review comment from: Comment on mode of inheritance: Most KCNJ11 seizure patients have heterozygous variants but PMID:27181099 report a patient with a homozygous variant in KCNJ11 (p.F315I) and congenital hyperinsulinism. The authors say the patient had severe hypoglycemia and seizure following birth, but no further seizure details are given. OMIM disorder 'Diabetes, permanent neonatal, with or without neurologic features (MIM:606176) has both AR and AD inheritance recorded.; to: Comment on mode of inheritance: Most KCNJ11 seizure patients have heterozygous variants but PMID:27181099 report a patient with a homozygous variant in KCNJ11 (p.F315I) and congenital hyperinsulinism. The authors say the patient had severe hypoglycemia and seizure following birth, but no further seizure details are given. OMIM disorder 'Diabetes, permanent neonatal, with or without neurologic features (MIM:606176) has both AR and AD inheritance recorded. Therefore based on PMID:27181099 plus OMIM plu review by West Midlands, Oxford and Wessex GLH, have updated MOI from 'monoallelic' to 'BOTH monoallelic and biallelic'.
13 Aug 2019	Early onset or syndromic epilepsy v1.201	KCNJ11	Rebecca Foulger Mode of inheritance for gene: KCNJ11 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
13 Aug 2019	Early onset or syndromic epilepsy v1.200	KCNJ11	Rebecca Foulger changed review comment from: Comment on mode of inheritance: Most seizure patients have heterozygous variants but PMID:27181099 report a patient with a homozygous variant in KCNJ11 (p.F315I) and congenital hyperinsulinism. The authors say the patient had severe hypoglycemia and seizure following birth, but no further seizure details are given. OMIM disorder 'Diabetes, permanent neonatal, with or without neurologic features (MIM:606176) has both AR and AD inheritance recorded.; to: Comment on mode of inheritance: Most KCNJ11 seizure patients have heterozygous variants but PMID:27181099 report a patient with a homozygous variant in KCNJ11 (p.F315I) and congenital hyperinsulinism. The authors say the patient had severe hypoglycemia and seizure following birth, but no further seizure details are given. OMIM disorder 'Diabetes, permanent neonatal, with or without neurologic features (MIM:606176) has both AR and AD inheritance recorded.
13 Aug 2019	Early onset or syndromic epilepsy v1.200	KCNJ11	Rebecca Foulger changed review comment from: Comment on mode of inheritance: Most seizure patients have heterozygous variants but PMID:27181099 report a patient with a homozygous variant in KCNJ11 (p.F315I) and congenital hyperinsulinism. The authors say the patient had severe hypoglycemia and seizure following birth, but no further seizure details are given.; to: Comment on mode of inheritance: Most seizure patients have heterozygous variants but PMID:27181099 report a patient with a homozygous variant in KCNJ11 (p.F315I) and congenital hyperinsulinism. The authors say the patient had severe hypoglycemia and seizure following birth, but no further seizure details are given. OMIM disorder 'Diabetes, permanent neonatal, with or without neurologic features (MIM:606176) has both AR and AD inheritance recorded.
13 Aug 2019	Early onset or syndromic epilepsy v1.200	KCNJ11	Rebecca Foulger Publications for gene: KCNJ11 were set to 25678012; 16670688; 16609879; 27681997; 17065345; 28943513
13 Aug 2019	Early onset or syndromic epilepsy v1.199	KCNJ11	Rebecca Foulger Added comment: Comment on mode of inheritance: Most seizure patients have heterozygous variants but PMID:27181099 report a patient with a homozygous variant in KCNJ11 (p.F315I) and congenital hyperinsulinism. The authors say the patient had severe hypoglycemia and seizure following birth, but no further seizure details are given.
13 Aug 2019	Early onset or syndromic epilepsy v1.199	KCNJ11	Rebecca Foulger Mode of inheritance for gene: KCNJ11 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
13 Aug 2019	Early onset or syndromic epilepsy v1.198	TUBB2A	Rebecca Foulger changed review comment from: Comment on list classification: Updated rating from Red to Green following advice from Helen Brittain: 3 unrelated cases from literature. Although not all with the genotype may develop seizures, there are sufficient cases of the epilepsy phenotype for inclusion on the panel.; to: Comment on list classification: Updated rating from Red to Green following advice from Helen Brittain: 3 unrelated cases from literature (two cases from PMID:24702957 and one from large-scale study PMID:25326637. Although not all with the genotype may develop seizures, there are sufficient cases of the epilepsy phenotype for inclusion on the panel.
13 Aug 2019	Early onset or syndromic epilepsy v1.198	HCN2	Rebecca Foulger changed review comment from: Comment on mode of inheritance: PMID:22131395: DiFrancesco et al. 2011 report a homozygous HCN2 variant (p.E515K) in a patient with idiopathic generalized epilepsy. Of 17 screened members of the same family, the proband was the only one affected and homozygous for the variant. This is the first evidence in humans for a single-point, homozygous loss-of-function mutation in HCN2 potentially associated with generalized epilepsy with recessive inheritance.; to: Comment on mode of inheritance: PMID:22131395: DiFrancesco et al. 2011 report a homozygous HCN2 variant (p.E515K) in a patient with idiopathic generalized epilepsy. Of 17 screened members of the same family, the proband was the only one affected and homozygous for the variant. This is the first evidence in humans for a single-point, homozygous loss-of-function mutation in HCN2 potentially associated with generalized epilepsy with recessive inheritance. Hence MOI listed as BOTH monoallelic and biallelic.
08 Aug 2019	Early onset or syndromic epilepsy v1.198	POLG2	Sarah Leigh Classified gene: POLG2 as Amber List (moderate evidence)
08 Aug 2019	Early onset or syndromic epilepsy v1.198	POLG2	Sarah Leigh Added comment: Comment on list classification: Single case of recessive epilepsy.
08 Aug 2019	Early onset or syndromic epilepsy v1.198	POLG2	Sarah Leigh Gene: polg2 has been classified as Amber List (Moderate Evidence).
08 Aug 2019	Early onset or syndromic epilepsy v1.197	POLG2	Sarah Leigh gene: POLG2 was added gene: POLG2 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: POLG2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: POLG2 were set to 31286721; 27592148; 30157269 Phenotypes for gene: POLG2 were set to Autosomal Recessive Epilepsy Family Without Ophthalmoplegia Review for gene: POLG2 was set to AMBER Added comment: Single case of Autosomal Recessive Epilepsy Family Without Ophthalmoplegia in a 27-year-old Pakistani male, who was homozygous for POLG2 c.694G>A, p.G232S. Both his parents were heterozygous for this variant, and none of them had liver disease, ophthalmoplegia, ptosis, nystagmus, or myopathy, and the parents showed no symptoms of epilepsy or ophthalmoplegia. Sources: Literature
08 Aug 2019	Early onset or syndromic epilepsy v1.196	AFF3	Konstantinos Varvagiannis changed review comment from: Voisin et al. (2019 - https://doi.org/10.1101/693937) report on 10 individuals with de novo missense AFF3 variants affecting a 9-amino-acid sequence (degron) important for the protein's degradation and summarize the phenotype of an additional individual previously described by Steichen-Gersdorf et al. (2008 - PMID: 18616733) with a 500 kb affecting only AFF3 (LAF4) and removing also this sequence. The phenotype of missense variants consisted of kidney anomalies, mesomelic dysplasia, seizures, hypertrichosis, intellectual disability and pulmonary problems and was overlapping with that of the deletion. [10 of 11 subjects exhibited severe developmental epileptic encephalopathy]. 9 probands harbored missense variants affecting the codon 258 while one individual had a variant affecting codon 260 [c.772G>T or p.Ala258Ser (x2), c.772G>A or p.Ala258Thr (x6), c.773C>T or p.Ala258Val (x1) and c.779T>G or p.(Val260Gly) (x1) - NM_001025108.1 / NP_001020279.1]. The deletion removed exons 4-13. AFF1-4 are ALF transcription factor paralogs, components of the transcriptional super elongation complex regulating expression of genes involved in neurogenesis and development. Using HEK293T cells expressing FLAG-tagged AFF3 (and AFF4) wt or mutants, accumulation of mutated forms was shown upon immunoblot. Aff3+/- and/or -/- mice exhibit skeletal defects. These were more pronounced in homozygous mice which demonstrated also some elements in favor of kidney dysfunction and/or metabolic deregulation and possible neurological dysfunction (signs of impaired hearing and diminished grip strength). Homozygous mice had CNS anomalies (enlarged lateral ventricles and decreased corpus callosum size) similar to some affected individuals, although these were not observed in another Aff3-/- model. Knock-in mice modeling the microdeletion and the Ala258Thr variant displayed lower mesomelic limb deformities and early lethality respectively [cited PMIDs : 21677750, 25660031, knock-in model was part of the present study]. Accumulation of the protein in zebrafish (by overexpression of the human wt AFF3 mRNA), led to morphological defects. Reanalysis of transcriptome data from previously generated HEK293T cell lines knocked down for AFF2, AFF3 and AFF4 by shRNAs (study) suggested that these transcription factors are not redundant. Finally, CHOPS syndrome (#616368) due to mutations of AFF4 also leading to increased protein stability presents a partially overlapping phenotype (incl. cognitive impairment) to that of AFF3. ---- In G2P, AFF3 is associated with Skeletal dysplasia with severe neurological disease (disease confidence : probable / ID and seizures among the assigned phenotypes). There is no associated phenotype in OMIM. ---- As a result this gene can be considered for inclusion in the epilepsy panel as green (relevant phenotype and severity, sufficient cases, evidence for accumulation similar to AFF4, animal models, etc) or amber (pending publication of the article). Sources: Literature; to: Voisin et al. (2019 - https://doi.org/10.1101/693937) report on 10 individuals with de novo missense AFF3 variants affecting a 9-amino-acid sequence (degron) important for the protein's degradation and summarize the phenotype of an additional individual previously described by Steichen-Gersdorf et al. (2008 - PMID: 18616733) with a 500 kb affecting only AFF3 (LAF4) and removing also this sequence. The phenotype of missense variants consisted of kidney anomalies, mesomelic dysplasia, seizures, hypertrichosis, intellectual disability and pulmonary problems and was overlapping with that of the deletion. [10 of 11 subjects exhibited severe developmental epileptic encephalopathy]. 9 probands harbored missense variants affecting the codon 258 while one individual had a variant affecting codon 260 [c.772G>T or p.Ala258Ser (x2), c.772G>A or p.Ala258Thr (x6), c.773C>T or p.Ala258Val (x1) and c.779T>G or p.(Val260Gly) (x1) - NM_001025108.1 / NP_001020279.1]. The deletion removed exons 4-13. AFF1-4 are ALF transcription factor paralogs, components of the transcriptional super elongation complex regulating expression of genes involved in neurogenesis and development. Using HEK293T cells expressing FLAG-tagged AFF3 (and AFF4) wt or mutants, accumulation of mutated forms was shown upon immunoblot. Aff3+/- and/or -/- mice exhibit skeletal defects. These were more pronounced in homozygous mice which demonstrated also some elements in favor of kidney dysfunction and/or metabolic deregulation and possible neurological dysfunction (signs of impaired hearing and diminished grip strength). Homozygous mice had CNS anomalies (enlarged lateral ventricles and decreased corpus callosum size) similar to some affected individuals, although these were not observed in another Aff3-/- model. Knock-in mice modeling the microdeletion and the Ala258Thr variant displayed lower mesomelic limb deformities and early lethality respectively [cited PMIDs : 21677750, 25660031, knock-in model was part of the present study]. Accumulation of the protein in zebrafish (by overexpression of the human wt AFF3 mRNA), led to morphological defects. Reanalysis of transcriptome data from previously generated HEK293T cell lines knocked down for AFF2, AFF3 and AFF4 by shRNAs (study) suggested that these transcription factors are not redundant. Finally, CHOPS syndrome (#616368) due to mutations of AFF4 also leading to increased protein stability presents a partially overlapping phenotype (incl. cognitive impairment) to that of AFF3. ---- In G2P, AFF3 is associated with Skeletal dysplasia with severe neurological disease (disease confidence : probable / ID and seizures among the assigned phenotypes). There is no associated phenotype in OMIM. ---- As a result this gene can be considered for inclusion in the epilepsy panel as green (relevant phenotype and severity, sufficient cases, evidence for accumulation similar to AFF4, animal models, etc) or amber (pending publication of the article). Sources: Literature --------------- Shimizu et al. (8/2019 - PMID: 31388108) describe an additional individual with de novo AFF3 missense variant. The phenotype overlaps with that summarized by Voisin et al. incl. mesomelic dysplasia with additional skeletal anomalies, bilateral kidney hypoplasia and severe DD at the age of 2.5 years. Seizures and pulmonary problems were not observed. Although a different RefSeq is used the variant is among those also reported by Voisin et al. [NM_002285.2:c.697G>A (p.Ala233Thr) corresponding to NM_001025108.1:c.772G>A (p.Ala258Thr)].
08 Aug 2019	Early onset or syndromic epilepsy v1.196	AFF3	Rebecca Foulger Tag missense tag was added to gene: AFF3. Tag watchlist tag was added to gene: AFF3.
08 Aug 2019	Early onset or syndromic epilepsy v1.196	AFF3	Rebecca Foulger Classified gene: AFF3 as Amber List (moderate evidence)
08 Aug 2019	Early onset or syndromic epilepsy v1.196	AFF3	Rebecca Foulger Gene: aff3 has been classified as Amber List (Moderate Evidence).
08 Aug 2019	Early onset or syndromic epilepsy v1.195	AFF3	Rebecca Foulger commented on gene: AFF3
08 Aug 2019	Early onset or syndromic epilepsy v1.195	WWOX	Rebecca Foulger commented on gene: WWOX: Usha Kini (Oxford Medical Genetics Laboratories) confirmed that WWOX should be on the epilepsy panel (personal communication via email on August 8th, 2019).
07 Aug 2019	Early onset or syndromic epilepsy v1.195	AFF3	Rebecca Foulger Phenotypes for gene: AFF3 were changed from Intellectual disability; Seizures; Abnormality of skeletal morphology; Abnormality of the urinary system; Hypertrichosis; Abnormality of the respiratory system to Intellectual disability; Seizures; KINSSHIP syndrome
07 Aug 2019	Early onset or syndromic epilepsy v1.194	PIGU	Rebecca Foulger commented on gene: PIGU
07 Aug 2019	Early onset or syndromic epilepsy v1.194	PIGU	Rebecca Foulger Tag missense tag was added to gene: PIGU.
07 Aug 2019	Early onset or syndromic epilepsy v1.194	GRIA2	Rebecca Foulger commented on gene: GRIA2: GRIA2 is not yet associated with a disorder in OMIM or Gene2Phenotype.
07 Aug 2019	Early onset or syndromic epilepsy v1.194	GRIA2	Rebecca Foulger commented on gene: GRIA2: PMID:8938126 (animal model): GluR2 heterozygous (+/−) mice showed reduced motor coordination but no sign of seizure activity as measured by observation, EEG, or post-mortem analysis.
07 Aug 2019	Early onset or syndromic epilepsy v1.194	GRIA2	Rebecca Foulger Phenotypes for gene: GRIA2 were changed from Intellectual disability; Seizures; Autism to Intellectual disability; Seizures; myoclonic seizures; status epilepticus; tonic-clonic seizures; focal seizures
07 Aug 2019	Early onset or syndromic epilepsy v1.193	GRIA2	Rebecca Foulger commented on gene: GRIA2
07 Aug 2019	Early onset or syndromic epilepsy v1.193	GRIA2	Konstantinos Varvagiannis gene: GRIA2 was added gene: GRIA2 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: GRIA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: GRIA2 were set to 31300657 Phenotypes for gene: GRIA2 were set to Intellectual disability; Seizures; Autism Penetrance for gene: GRIA2 were set to unknown Review for gene: GRIA2 was set to AMBER Added comment: There is a recent publication by Salpietro et al. (2019 - PMID: 31300657) reporting on 28 unrelated individuals. Seizures were observed in 12/28 (~40%), so the gene may also be relevant for the current panel. The phenotype overall corresponds to a NDD disorder with DD, ID (universal feature in those with appropriate age for evaluation, relevant severity), ASD, Rett-like features and seizures. All types of variants were reported (15 missense, 2 splice-site, 1 in-frame del, 1 stopgain, 2 frameshift ones, 3 CNVs spanning GRIA2 and other genes, the latter more tolerant to LoF). The role of this gene (encoding AMPA receptor GluA2 subunit), functional studies (loss of function demonstrated for the majority of mutations, though by multiple molecular mechanisms), overlapping phenotype with disorders due to other ionotropic glutamate receptor subunit genes (eg. GRIA3/4 - ID with or without seizures), animal models (PMID cited: 8938126) are among the arguments provided. Sources: Literature
07 Aug 2019	Early onset or syndromic epilepsy v1.193	AFF3	Konstantinos Varvagiannis gene: AFF3 was added gene: AFF3 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: AFF3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: AFF3 were set to https://doi.org/10.1101/693937; 18616733 Phenotypes for gene: AFF3 were set to Intellectual disability; Seizures; Abnormality of skeletal morphology; Abnormality of the urinary system; Hypertrichosis; Abnormality of the respiratory system Penetrance for gene: AFF3 were set to unknown Mode of pathogenicity for gene: AFF3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: AFF3 was set to GREEN Added comment: Voisin et al. (2019 - https://doi.org/10.1101/693937) report on 10 individuals with de novo missense AFF3 variants affecting a 9-amino-acid sequence (degron) important for the protein's degradation and summarize the phenotype of an additional individual previously described by Steichen-Gersdorf et al. (2008 - PMID: 18616733) with a 500 kb affecting only AFF3 (LAF4) and removing also this sequence. The phenotype of missense variants consisted of kidney anomalies, mesomelic dysplasia, seizures, hypertrichosis, intellectual disability and pulmonary problems and was overlapping with that of the deletion. [10 of 11 subjects exhibited severe developmental epileptic encephalopathy]. 9 probands harbored missense variants affecting the codon 258 while one individual had a variant affecting codon 260 [c.772G>T or p.Ala258Ser (x2), c.772G>A or p.Ala258Thr (x6), c.773C>T or p.Ala258Val (x1) and c.779T>G or p.(Val260Gly) (x1) - NM_001025108.1 / NP_001020279.1]. The deletion removed exons 4-13. AFF1-4 are ALF transcription factor paralogs, components of the transcriptional super elongation complex regulating expression of genes involved in neurogenesis and development. Using HEK293T cells expressing FLAG-tagged AFF3 (and AFF4) wt or mutants, accumulation of mutated forms was shown upon immunoblot. Aff3+/- and/or -/- mice exhibit skeletal defects. These were more pronounced in homozygous mice which demonstrated also some elements in favor of kidney dysfunction and/or metabolic deregulation and possible neurological dysfunction (signs of impaired hearing and diminished grip strength). Homozygous mice had CNS anomalies (enlarged lateral ventricles and decreased corpus callosum size) similar to some affected individuals, although these were not observed in another Aff3-/- model. Knock-in mice modeling the microdeletion and the Ala258Thr variant displayed lower mesomelic limb deformities and early lethality respectively [cited PMIDs : 21677750, 25660031, knock-in model was part of the present study]. Accumulation of the protein in zebrafish (by overexpression of the human wt AFF3 mRNA), led to morphological defects. Reanalysis of transcriptome data from previously generated HEK293T cell lines knocked down for AFF2, AFF3 and AFF4 by shRNAs (study) suggested that these transcription factors are not redundant. Finally, CHOPS syndrome (#616368) due to mutations of AFF4 also leading to increased protein stability presents a partially overlapping phenotype (incl. cognitive impairment) to that of AFF3. ---- In G2P, AFF3 is associated with Skeletal dysplasia with severe neurological disease (disease confidence : probable / ID and seizures among the assigned phenotypes). There is no associated phenotype in OMIM. ---- As a result this gene can be considered for inclusion in the epilepsy panel as green (relevant phenotype and severity, sufficient cases, evidence for accumulation similar to AFF4, animal models, etc) or amber (pending publication of the article). Sources: Literature
07 Aug 2019	Early onset or syndromic epilepsy v1.193	PIGU	Konstantinos Varvagiannis gene: PIGU was added gene: PIGU was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: PIGU was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIGU were set to 31353022 Phenotypes for gene: PIGU were set to Global developmental delay; Intellectual disability; Seizures; Cerebral atrophy; Cerebellar hypoplasia; Scoliosis Penetrance for gene: PIGU were set to Complete Review for gene: PIGU was set to GREEN Added comment: Knaus et al. (2019 - PMID: 31353022) report on 5 affected individuals (from 3 unrelated families) with biallelic pathogenic PIGU variants. Common features included tone abnormalities, global DD, ID, seizures, CNS anomalies (cerebral atrophy and/or cerebellar hypoplasia), scoliosis. Affected individuals presented also with facial similarities. DD/ID were universal features and their severity appears to be relevant to the panel. Seizures were also reported in all individuals (myoclonic in 3, for whom this was specified). ALP was normal in all. Three individuals from 2 non-consanguineous families (one from Norway, the other not specified) were homozygous for a missense variant NM_080476.4:c.1149C>A (or p.Asn383Lys) present with an AF of 7/277197 in Europeans. Two individuals born to consanguineous parents from Turkey were homozygous for another missense variant (c.209T>A or p.Ile70Lys - same RefSeq). Segregation analyses in parents and unaffected sibs were carried out. PIGU encodes a subunit of the GPI transaminidase, a heteropentameric complex (other subunits encoded by PIGK, PIGS, PIGT and GPAA1) that mediates attachment in the endoplasmic reticulum of glycosylphosphatidylinositol (GPI) to the C-termini of proteins which are subsequently anchored to the cell surface. Pathogenic variants in 18 of 29 genes implicated in biosynthesis of the GPI anchor have been identified as a cause of GPI biosynthesis disorders, with ID and seizures as principal features. Mutations in other genes encoding components of the GPI transaminidase complex (GPAA1, PIGT and PIGS) lead to neurodevelopmental disorders. Functional impairment of PIGU was supported by flow-cytometric analysis showing significant reduction of cell surface expression of GPI anchored proteins (mainly FLAER, CD16 and CD24) on granulocytes from affected individuals. In addition accumulation of free GPI anchors on the cell surface of B cells from affected individuals further suggested deficiency of the GPI transaminidase. Transient expression of mutant (Asn383Lys) protein failed to rescue expression of GPI-APs to the same extent as wt in a CHO cell line deficient for PIGU. Feature analysis demonstrated similarities among individuals with mutations in other genes of the GPI transamidase complex (GPAA1 and PIGT) as well as with GPI biosynthesis disorders. Facial analysis was also suggestive of facial similarities between individuals with GPAA1 and PIGU mutations. PIGU is not associated with any phenotype in OMIM or G2P. As a result this gene can be considered for inclusion in the ID and epilepsy panels probably as green (3 families, ID of relevant severity and seizures in all affected individuals, known group of disorders and supportive evidence) or amber. Sources: Literature
07 Aug 2019	Early onset or syndromic epilepsy v1.193	WDR37	Konstantinos Varvagiannis gene: WDR37 was added gene: WDR37 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: WDR37 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: WDR37 were set to 31327510; 31327508 Phenotypes for gene: WDR37 were set to Global developmental delay; Intellectual disability; Seizures; Abnormality of the eye; Abnormality of nervous system morphology; Hearing abnormality; Abnormality of the cardiovascular system; Abnormality of the skeletal system; Abnormality of the genitourinary system Penetrance for gene: WDR37 were set to unknown Mode of pathogenicity for gene: WDR37 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: WDR37 was set to GREEN Added comment: Two concurrent publications by Reis et al. and Kanca et al. (2019 - PMIDs: 31327510, 31327508) report on the phenotype of individuals with de novo WDR37 mutations. The study by Reis et al. provides clinical details on 4 affected individuals, while 5 further are described by Kanca et al. 4 different de novo variants were reported in these individuals who appear to be unrelated in (and between) the 2 studies [NM_014023.3]: - c.356C>T (p.Ser119Phe) [Reis indiv. 1 - 3y, Kanca proband 3 - 5m2w] - c.389C>T (p.Thr130Ile) [Reis indiv. 2 - 22m , Kanca proband 5 - 6 w] - c.374C>T (p.Thr125Ile) [Reis indiv. 3 - 8y , Kanca proband 1 - 7y] - c.386C>G (p.Ser129Cys) [Reis indiv. 4 - unkn age, Kanca probands 2 and 4, 6.5y and 19y] Common features included DD/ID (severity relevant for the current panel), seizures (9/9), ocular anomalies (corneal opacity/Peters anomaly, coloboma, microphthalmia etc.) and variable brain, hearing, cardiovascular, skeletal and genitourinary anomalies. Some facial and/or other dysmorphic features (incl. excess nuchal skin / webbed neck) were also frequent among affected individuals. Feeding difficulties and growth deficiency were also among the features observed. The function of WDR37 is not known. Variants demonstrated comparable protein levels and cellular localization compared to wt. Reis et al. provide evidence using CRISPR-Cas9 mediated genome editing in zebrafish, to introduce the Ser129Cys variant observed in affected individuals as well as novel missense and frameshift variants. Poor growth (similar to the human phenotype) and larval lethality were noted for missense variants. Head size was proportionately small. Ocular (coloboma/corneal) or craniofacial anomalies were not observed. Zebrafish heterozygous for LoF variants survived to adulthood. Based on these a dominant-negative mechanism was postulated for missense alleles. RNA-seq analysis in zebrafish showed upregulation of cholesterol biosynthesis pathways (among the most dysregulated ones). Previous data in mice, suggest a broad expression pattern for Wdr37 with enrichment in ocular and brain tissues, significant associations in homozygous mutant mice for decreased body weight, grip strength, skeletal anomalies and possible increase (p =< 0.05) in ocular (lens/corneal) and other anomalies [BioGPS and International Mouse Phenotyping Consortium cited]. CG12333 loss (the Drosophila WDR37 ortholog) causes increased bang sensitivity in flies (analogous to the human epilepsy phenotype), defects in copulation and grip strength, phenotypes that were rescued by human reference but not variant cDNAs. As discussed by Kanca et al. based on data from Drosophila and mice, limited phenotypic similarity of CNVs spanning WDR37 and adjacent genes with the reported individuals and the presence of LoF variants in control populations haploinsufficiency appears unlikely. Gain-of-function is also unlikely, as expression of human variants in flies did not exacerbate the observed phenotypes. A dominant-negative effect is again proposed. WDR37 is not associated with any phenotype in OMIM/G2P. As a result WDR37 can be considered for inclusion in the ID and epilepsy panels with green (relevant phenotype, sufficient cases, animal models) or amber rating. Sources: Literature
06 Aug 2019	Early onset or syndromic epilepsy v1.193	ATN1_CAG	Rebecca Foulger Source NHS GMS was added to STR: ATN1_CAG.
06 Aug 2019	Early onset or syndromic epilepsy v1.192	CSTB_CCCCGCCCCGCG	Rebecca Foulger Source NHS GMS was added to STR: CSTB_CCCCGCCCCGCG.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CSTB_CCCCGCCCCGCG	Rebecca Foulger commented on STR: CSTB_CCCCGCCCCGCG
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ATN1_CAG	Rebecca Foulger commented on STR: ATN1_CAG
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CUL4B	Rebecca Foulger Source Wessex and West Midlands GLH was added to CUL4B.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TUBA3E	Rebecca Foulger Source Wessex and West Midlands GLH was added to TUBA3E.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SLC6A5	Rebecca Foulger Source Wessex and West Midlands GLH was added to SLC6A5.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SHH	Rebecca Foulger Source Wessex and West Midlands GLH was added to SHH.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SEC24D	Rebecca Foulger Source Wessex and West Midlands GLH was added to SEC24D.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SCN2B	Rebecca Foulger Source Wessex and West Midlands GLH was added to SCN2B.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RYR3	Rebecca Foulger Source Wessex and West Midlands GLH was added to RYR3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RUBCN	Rebecca Foulger Source Wessex and West Midlands GLH was added to RUBCN.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PSMB8	Rebecca Foulger Source Wessex and West Midlands GLH was added to PSMB8.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PRICKLE2	Rebecca Foulger Source Wessex and West Midlands GLH was added to PRICKLE2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PCDHB4	Rebecca Foulger Source Wessex and West Midlands GLH was added to PCDHB4.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NRAS	Rebecca Foulger Source Wessex and West Midlands GLH was added to NRAS.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NID1	Rebecca Foulger Source Wessex and West Midlands GLH was added to NID1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NDUFA11	Rebecca Foulger Source Wessex and West Midlands GLH was added to NDUFA11.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MT-TL1	Rebecca Foulger Source Wessex and West Midlands GLH was added to MT-TL1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MATN4	Rebecca Foulger Source Wessex and West Midlands GLH was added to MATN4.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MAPK10	Rebecca Foulger Source Wessex and West Midlands GLH was added to MAPK10.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KAT5	Rebecca Foulger Source Wessex and West Midlands GLH was added to KAT5.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	INO80	Rebecca Foulger Source Wessex and West Midlands GLH was added to INO80.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	H3F3B	Rebecca Foulger Source Wessex and West Midlands GLH was added to H3F3B.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	H3F3A	Rebecca Foulger Source Wessex and West Midlands GLH was added to H3F3A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GLRB	Rebecca Foulger Source Wessex and West Midlands GLH was added to GLRB.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GCSH	Rebecca Foulger Source Wessex and West Midlands GLH was added to GCSH.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GATM	Rebecca Foulger Source Wessex and West Midlands GLH was added to GATM.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GATAD2B	Rebecca Foulger Source Wessex and West Midlands GLH was added to GATAD2B.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GAL	Rebecca Foulger Source Wessex and West Midlands GLH was added to GAL.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GABRD	Rebecca Foulger Source Wessex and West Midlands GLH was added to GABRD.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	FTL	Rebecca Foulger Source Wessex and West Midlands GLH was added to FTL.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	FIG4	Rebecca Foulger Source Wessex and West Midlands GLH was added to FIG4.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DMBX1	Rebecca Foulger Source Wessex and West Midlands GLH was added to DMBX1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CYP27A1	Rebecca Foulger Source Wessex and West Midlands GLH was added to CYP27A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CSNK1G1	Rebecca Foulger Source Wessex and West Midlands GLH was added to CSNK1G1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CRH	Rebecca Foulger Source Wessex and West Midlands GLH was added to CRH.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CNTN2	Rebecca Foulger Source Wessex and West Midlands GLH was added to CNTN2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CLN6	Rebecca Foulger Source Wessex and West Midlands GLH was added to CLN6.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CLN5	Rebecca Foulger Source Wessex and West Midlands GLH was added to CLN5.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CLCN2	Rebecca Foulger Source Wessex and West Midlands GLH was added to CLCN2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CBL	Rebecca Foulger Source Wessex and West Midlands GLH was added to CBL.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CASR	Rebecca Foulger Source Wessex and West Midlands GLH was added to CASR.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CAMK2G	Rebecca Foulger Source Wessex and West Midlands GLH was added to CAMK2G.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CACNB4	Rebecca Foulger Source Wessex and West Midlands GLH was added to CACNB4.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ASAH1	Rebecca Foulger Source Wessex and West Midlands GLH was added to ASAH1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ALG2	Rebecca Foulger Source Wessex and West Midlands GLH was added to ALG2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ALG12	Rebecca Foulger Source Wessex and West Midlands GLH was added to ALG12.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ADGRV1	Rebecca Foulger Source Wessex and West Midlands GLH was added to ADGRV1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	AARS2	Rebecca Foulger Source Wessex and West Midlands GLH was added to AARS2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	VLDLR	Rebecca Foulger Source Wessex and West Midlands GLH was added to VLDLR.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	UFC1	Rebecca Foulger Source Wessex and West Midlands GLH was added to UFC1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TXNRD1	Rebecca Foulger Source Wessex and West Midlands GLH was added to TXNRD1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TUBB	Rebecca Foulger Source Wessex and West Midlands GLH was added to TUBB.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TUBA8	Rebecca Foulger Source Wessex and West Midlands GLH was added to TUBA8.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TSFM	Rebecca Foulger Source Wessex and West Midlands GLH was added to TSFM.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TSEN34	Rebecca Foulger Source Wessex and West Midlands GLH was added to TSEN34.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TSEN15	Rebecca Foulger Source Wessex and West Midlands GLH was added to TSEN15.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TRIP13	Rebecca Foulger Source Wessex and West Midlands GLH was added to TRIP13.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TRAPPC6B	Rebecca Foulger Source Wessex and West Midlands GLH was added to TRAPPC6B.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TRAPPC12	Rebecca Foulger Source Wessex and West Midlands GLH was added to TRAPPC12.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TRAF7	Rebecca Foulger Source Wessex and West Midlands GLH was added to TRAF7.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TNK2	Rebecca Foulger Source Wessex and West Midlands GLH was added to TNK2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TIMM50	Rebecca Foulger Source Wessex and West Midlands GLH was added to TIMM50.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TFE3	Rebecca Foulger Source Wessex and West Midlands GLH was added to TFE3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TELO2	Rebecca Foulger Source Wessex and West Midlands GLH was added to TELO2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TBC1D20	Rebecca Foulger Source Wessex and West Midlands GLH was added to TBC1D20.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SUCLG1	Rebecca Foulger Source Wessex and West Midlands GLH was added to SUCLG1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ST3GAL3	Rebecca Foulger Source Wessex and West Midlands GLH was added to ST3GAL3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SRPX2	Rebecca Foulger Source Wessex and West Midlands GLH was added to SRPX2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SPR	Rebecca Foulger Source Wessex and West Midlands GLH was added to SPR.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SNIP1	Rebecca Foulger Source Wessex and West Midlands GLH was added to SNIP1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SMC1A	Rebecca Foulger Source Wessex and West Midlands GLH was added to SMC1A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SLC45A1	Rebecca Foulger Source Wessex and West Midlands GLH was added to SLC45A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SLC35A1	Rebecca Foulger Source Wessex and West Midlands GLH was added to SLC35A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SIX3	Rebecca Foulger Source Wessex and West Midlands GLH was added to SIX3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SETD1B	Rebecca Foulger Source Wessex and West Midlands GLH was added to SETD1B.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SDHA	Rebecca Foulger Source Wessex and West Midlands GLH was added to SDHA.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RYR2	Rebecca Foulger Source Wessex and West Midlands GLH was added to RYR2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RUSC2	Rebecca Foulger Source Wessex and West Midlands GLH was added to RUSC2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RRM2B	Rebecca Foulger Source Wessex and West Midlands GLH was added to RRM2B.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RPIA	Rebecca Foulger Source Wessex and West Midlands GLH was added to RPIA.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RNU4ATAC	Rebecca Foulger Source Wessex and West Midlands GLH was added to RNU4ATAC.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RAB3GAP2	Rebecca Foulger Source Wessex and West Midlands GLH was added to RAB3GAP2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RAB3GAP1	Rebecca Foulger Source Wessex and West Midlands GLH was added to RAB3GAP1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PTF1A	Rebecca Foulger Source Wessex and West Midlands GLH was added to PTF1A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PSPH	Rebecca Foulger Source Wessex and West Midlands GLH was added to PSPH.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PSAT1	Rebecca Foulger Source Wessex and West Midlands GLH was added to PSAT1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	POMT2	Rebecca Foulger Source Wessex and West Midlands GLH was added to POMT2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PIGQ	Rebecca Foulger Source Wessex and West Midlands GLH was added to PIGQ.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PIGH	Rebecca Foulger Source Wessex and West Midlands GLH was added to PIGH.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PIGC	Rebecca Foulger Source Wessex and West Midlands GLH was added to PIGC.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PEX5	Rebecca Foulger Source Wessex and West Midlands GLH was added to PEX5.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PDSS2	Rebecca Foulger Source Wessex and West Midlands GLH was added to PDSS2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PCLO	Rebecca Foulger Source Wessex and West Midlands GLH was added to PCLO.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	OTX2	Rebecca Foulger Source Wessex and West Midlands GLH was added to OTX2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NUBPL	Rebecca Foulger Source Wessex and West Midlands GLH was added to NUBPL.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NPRL2	Rebecca Foulger Source Wessex and West Midlands GLH was added to NPRL2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NEDD4L	Rebecca Foulger Source Wessex and West Midlands GLH was added to NEDD4L.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NECAP1	Rebecca Foulger Source Wessex and West Midlands GLH was added to NECAP1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NDUFS7	Rebecca Foulger Source Wessex and West Midlands GLH was added to NDUFS7.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NDUFS6	Rebecca Foulger Source Wessex and West Midlands GLH was added to NDUFS6.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NDUFS2	Rebecca Foulger Source Wessex and West Midlands GLH was added to NDUFS2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NDUFS1	Rebecca Foulger Source Wessex and West Midlands GLH was added to NDUFS1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NDUFAF4	Rebecca Foulger Source Wessex and West Midlands GLH was added to NDUFAF4.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NDUFAF3	Rebecca Foulger Source Wessex and West Midlands GLH was added to NDUFAF3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NDUFA2	Rebecca Foulger Source Wessex and West Midlands GLH was added to NDUFA2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NDP	Rebecca Foulger Source Wessex and West Midlands GLH was added to NDP.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MED17	Rebecca Foulger Source Wessex and West Midlands GLH was added to MED17.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MAST1	Rebecca Foulger Source Wessex and West Midlands GLH was added to MAST1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MANBA	Rebecca Foulger Source Wessex and West Midlands GLH was added to MANBA.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	LNPK	Rebecca Foulger Source Wessex and West Midlands GLH was added to LNPK.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	LIPT2	Rebecca Foulger Source Wessex and West Midlands GLH was added to LIPT2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	LARGE1	Rebecca Foulger Source Wessex and West Midlands GLH was added to LARGE1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KPTN	Rebecca Foulger Source Wessex and West Midlands GLH was added to KPTN.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KIAA1109	Rebecca Foulger Source Wessex and West Midlands GLH was added to KIAA1109.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KCNMA1	Rebecca Foulger Source Wessex and West Midlands GLH was added to KCNMA1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ISPD	Rebecca Foulger Source Wessex and West Midlands GLH was added to ISPD.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	HSPD1	Rebecca Foulger Source Wessex and West Midlands GLH was added to HSPD1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	HPRT1	Rebecca Foulger Source Wessex and West Midlands GLH was added to HPRT1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	HOXA1	Rebecca Foulger Source Wessex and West Midlands GLH was added to HOXA1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	HEXB	Rebecca Foulger Source Wessex and West Midlands GLH was added to HEXB.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	HCCS	Rebecca Foulger Source Wessex and West Midlands GLH was added to HCCS.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GTPBP3	Rebecca Foulger Source Wessex and West Midlands GLH was added to GTPBP3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GLRA1	Rebecca Foulger Source Wessex and West Midlands GLH was added to GLRA1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GLI3	Rebecca Foulger Source Wessex and West Midlands GLH was added to GLI3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	FOXRED1	Rebecca Foulger Source Wessex and West Midlands GLH was added to FOXRED1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	FKRP	Rebecca Foulger Source Wessex and West Midlands GLH was added to FKRP.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	FASTKD2	Rebecca Foulger Source Wessex and West Midlands GLH was added to FASTKD2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	EIF2B3	Rebecca Foulger Source Wessex and West Midlands GLH was added to EIF2B3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	EIF2B1	Rebecca Foulger Source Wessex and West Midlands GLH was added to EIF2B1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	EFHC1	Rebecca Foulger Source Wessex and West Midlands GLH was added to EFHC1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DPM2	Rebecca Foulger Source Wessex and West Midlands GLH was added to DPM2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DOLK	Rebecca Foulger Source Wessex and West Midlands GLH was added to DOLK.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DNAJC6	Rebecca Foulger Source Wessex and West Midlands GLH was added to DNAJC6.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DHCR24	Rebecca Foulger Source Wessex and West Midlands GLH was added to DHCR24.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DBT	Rebecca Foulger Source Wessex and West Midlands GLH was added to DBT.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CUX2	Rebecca Foulger Source Wessex and West Midlands GLH was added to CUX2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CSNK2B	Rebecca Foulger Source Wessex and West Midlands GLH was added to CSNK2B.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	COX15	Rebecca Foulger Source Wessex and West Midlands GLH was added to COX15.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	COX10	Rebecca Foulger Source Wessex and West Midlands GLH was added to COX10.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	COQ6	Rebecca Foulger Source Wessex and West Midlands GLH was added to COQ6.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	COG8	Rebecca Foulger Source Wessex and West Midlands GLH was added to COG8.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	COG6	Rebecca Foulger Source Wessex and West Midlands GLH was added to COG6.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	COG4	Rebecca Foulger Source Wessex and West Midlands GLH was added to COG4.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CNPY3	Rebecca Foulger Source Wessex and West Midlands GLH was added to CNPY3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CCND2	Rebecca Foulger Source Wessex and West Midlands GLH was added to CCND2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CCDC88C	Rebecca Foulger Source Wessex and West Midlands GLH was added to CCDC88C.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CCDC88A	Rebecca Foulger Source Wessex and West Midlands GLH was added to CCDC88A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CACNA2D2	Rebecca Foulger Source Wessex and West Midlands GLH was added to CACNA2D2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CACNA1H	Rebecca Foulger Source Wessex and West Midlands GLH was added to CACNA1H.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ATP6AP2	Rebecca Foulger Source Wessex and West Midlands GLH was added to ATP6AP2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ATP5A1	Rebecca Foulger Source Wessex and West Midlands GLH was added to ATP5A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ATP1A2	Rebecca Foulger Source Wessex and West Midlands GLH was added to ATP1A2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ADAT3	Rebecca Foulger Source Wessex and West Midlands GLH was added to ADAT3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ZBTB18	Rebecca Foulger Source Wessex and West Midlands GLH was added to ZBTB18.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	YWHAG	Rebecca Foulger Source Wessex and West Midlands GLH was added to YWHAG.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	WDR73	Rebecca Foulger Source Wessex and West Midlands GLH was added to WDR73.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	WDR62	Rebecca Foulger Source Wessex and West Midlands GLH was added to WDR62.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	WASF1	Rebecca Foulger Source Wessex and West Midlands GLH was added to WASF1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	VARS	Rebecca Foulger Source Wessex and West Midlands GLH was added to VARS.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	UNC80	Rebecca Foulger Source Wessex and West Midlands GLH was added to UNC80.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	UFM1	Rebecca Foulger Source Wessex and West Midlands GLH was added to UFM1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	UBA5	Rebecca Foulger Source Wessex and West Midlands GLH was added to UBA5.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TUBG1	Rebecca Foulger Source Wessex and West Midlands GLH was added to TUBG1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TUBB4A	Rebecca Foulger Source Wessex and West Midlands GLH was added to TUBB4A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TUBB3	Rebecca Foulger Source Wessex and West Midlands GLH was added to TUBB3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TUBB2B	Rebecca Foulger Source Wessex and West Midlands GLH was added to TUBB2B.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TUBB2A	Rebecca Foulger Source Wessex and West Midlands GLH was added to TUBB2A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TUBA1A	Rebecca Foulger Source Wessex and West Midlands GLH was added to TUBA1A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TSEN54	Rebecca Foulger Source Wessex and West Midlands GLH was added to TSEN54.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TSEN2	Rebecca Foulger Source Wessex and West Midlands GLH was added to TSEN2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TSC2	Rebecca Foulger Source Wessex and West Midlands GLH was added to TSC2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TSC1	Rebecca Foulger Source Wessex and West Midlands GLH was added to TSC1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TRIM8	Rebecca Foulger Source Wessex and West Midlands GLH was added to TRIM8.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TREX1	Rebecca Foulger Source Wessex and West Midlands GLH was added to TREX1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TMEM70	Rebecca Foulger Source Wessex and West Midlands GLH was added to TMEM70.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TBL1XR1	Rebecca Foulger Source Wessex and West Midlands GLH was added to TBL1XR1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TBCK	Rebecca Foulger Source Wessex and West Midlands GLH was added to TBCK.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TBCD	Rebecca Foulger Source Wessex and West Midlands GLH was added to TBCD.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TANGO2	Rebecca Foulger Source Wessex and West Midlands GLH was added to TANGO2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SYN1	Rebecca Foulger Source Wessex and West Midlands GLH was added to SYN1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SURF1	Rebecca Foulger Source Wessex and West Midlands GLH was added to SURF1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SUCLA2	Rebecca Foulger Source Wessex and West Midlands GLH was added to SUCLA2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	STAMBP	Rebecca Foulger Source Wessex and West Midlands GLH was added to STAMBP.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	STAG1	Rebecca Foulger Source Wessex and West Midlands GLH was added to STAG1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ST3GAL5	Rebecca Foulger Source Wessex and West Midlands GLH was added to ST3GAL5.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SNORD118	Rebecca Foulger Source Wessex and West Midlands GLH was added to SNORD118.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SMS	Rebecca Foulger Source Wessex and West Midlands GLH was added to SMS.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SMARCA2	Rebecca Foulger Source Wessex and West Midlands GLH was added to SMARCA2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SLC6A8	Rebecca Foulger Source Wessex and West Midlands GLH was added to SLC6A8.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SLC25A12	Rebecca Foulger Source Wessex and West Midlands GLH was added to SLC25A12.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SLC1A4	Rebecca Foulger Source Wessex and West Midlands GLH was added to SLC1A4.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SETBP1	Rebecca Foulger Source Wessex and West Midlands GLH was added to SETBP1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SEPSECS	Rebecca Foulger Source Wessex and West Midlands GLH was added to SEPSECS.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SCO2	Rebecca Foulger Source Wessex and West Midlands GLH was added to SCO2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SCO1	Rebecca Foulger Source Wessex and West Midlands GLH was added to SCO1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SCN3A	Rebecca Foulger Source Wessex and West Midlands GLH was added to SCN3A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SAMHD1	Rebecca Foulger Source Wessex and West Midlands GLH was added to SAMHD1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RTTN	Rebecca Foulger Source Wessex and West Midlands GLH was added to RTTN.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RTN4IP1	Rebecca Foulger Source Wessex and West Midlands GLH was added to RTN4IP1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RORB	Rebecca Foulger Source Wessex and West Midlands GLH was added to RORB.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RORA	Rebecca Foulger Source Wessex and West Midlands GLH was added to RORA.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ROGDI	Rebecca Foulger Source Wessex and West Midlands GLH was added to ROGDI.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RNASET2	Rebecca Foulger Source Wessex and West Midlands GLH was added to RNASET2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RNASEH2C	Rebecca Foulger Source Wessex and West Midlands GLH was added to RNASEH2C.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RNASEH2B	Rebecca Foulger Source Wessex and West Midlands GLH was added to RNASEH2B.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RNASEH2A	Rebecca Foulger Source Wessex and West Midlands GLH was added to RNASEH2A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RMND1	Rebecca Foulger Source Wessex and West Midlands GLH was added to RMND1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RHOBTB2	Rebecca Foulger Source Wessex and West Midlands GLH was added to RHOBTB2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RFT1	Rebecca Foulger Source Wessex and West Midlands GLH was added to RFT1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RELN	Rebecca Foulger Source Wessex and West Midlands GLH was added to RELN.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RARS2	Rebecca Foulger Source Wessex and West Midlands GLH was added to RARS2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RALA	Rebecca Foulger Source Wessex and West Midlands GLH was added to RALA.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RAB18	Rebecca Foulger Source Wessex and West Midlands GLH was added to RAB18.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RAB11B	Rebecca Foulger Source Wessex and West Midlands GLH was added to RAB11B.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	QDPR	Rebecca Foulger Source Wessex and West Midlands GLH was added to QDPR.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PTS	Rebecca Foulger Source Wessex and West Midlands GLH was added to PTS.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PTPN23	Rebecca Foulger Source Wessex and West Midlands GLH was added to PTPN23.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PTEN	Rebecca Foulger Source Wessex and West Midlands GLH was added to PTEN.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PSAP	Rebecca Foulger Source Wessex and West Midlands GLH was added to PSAP.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PRMT7	Rebecca Foulger Source Wessex and West Midlands GLH was added to PRMT7.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PRICKLE1	Rebecca Foulger Source Wessex and West Midlands GLH was added to PRICKLE1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PPT1	Rebecca Foulger Source Wessex and West Midlands GLH was added to PPT1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PPP3CA	Rebecca Foulger Source Wessex and West Midlands GLH was added to PPP3CA.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	POMT1	Rebecca Foulger Source Wessex and West Midlands GLH was added to POMT1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	POMGNT1	Rebecca Foulger Source Wessex and West Midlands GLH was added to POMGNT1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PMM2	Rebecca Foulger Source Wessex and West Midlands GLH was added to PMM2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PLAA	Rebecca Foulger Source Wessex and West Midlands GLH was added to PLAA.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PIK3R2	Rebecca Foulger Source Wessex and West Midlands GLH was added to PIK3R2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PIK3CA	Rebecca Foulger Source Wessex and West Midlands GLH was added to PIK3CA.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PIGW	Rebecca Foulger Source Wessex and West Midlands GLH was added to PIGW.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PIGO	Rebecca Foulger Source Wessex and West Midlands GLH was added to PIGO.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PIGG	Rebecca Foulger Source Wessex and West Midlands GLH was added to PIGG.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PHGDH	Rebecca Foulger Source Wessex and West Midlands GLH was added to PHGDH.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PHACTR1	Rebecca Foulger Source Wessex and West Midlands GLH was added to PHACTR1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PEX7	Rebecca Foulger Source Wessex and West Midlands GLH was added to PEX7.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PEX6	Rebecca Foulger Source Wessex and West Midlands GLH was added to PEX6.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PEX3	Rebecca Foulger Source Wessex and West Midlands GLH was added to PEX3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PEX2	Rebecca Foulger Source Wessex and West Midlands GLH was added to PEX2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PEX19	Rebecca Foulger Source Wessex and West Midlands GLH was added to PEX19.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PEX13	Rebecca Foulger Source Wessex and West Midlands GLH was added to PEX13.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PEX12	Rebecca Foulger Source Wessex and West Midlands GLH was added to PEX12.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PEX10	Rebecca Foulger Source Wessex and West Midlands GLH was added to PEX10.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PEX1	Rebecca Foulger Source Wessex and West Midlands GLH was added to PEX1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PET100	Rebecca Foulger Source Wessex and West Midlands GLH was added to PET100.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PDHX	Rebecca Foulger Source Wessex and West Midlands GLH was added to PDHX.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PDHA1	Rebecca Foulger Source Wessex and West Midlands GLH was added to PDHA1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PCDH12	Rebecca Foulger Source Wessex and West Midlands GLH was added to PCDH12.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PCCB	Rebecca Foulger Source Wessex and West Midlands GLH was added to PCCB.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PCCA	Rebecca Foulger Source Wessex and West Midlands GLH was added to PCCA.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PAH	Rebecca Foulger Source Wessex and West Midlands GLH was added to PAH.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PAFAH1B1	Rebecca Foulger Source Wessex and West Midlands GLH was added to PAFAH1B1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PACS2	Rebecca Foulger Source Wessex and West Midlands GLH was added to PACS2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PACS1	Rebecca Foulger Source Wessex and West Midlands GLH was added to PACS1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	OTUD6B	Rebecca Foulger Source Wessex and West Midlands GLH was added to OTUD6B.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	OPHN1	Rebecca Foulger Source Wessex and West Midlands GLH was added to OPHN1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	OCLN	Rebecca Foulger Source Wessex and West Midlands GLH was added to OCLN.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NTRK2	Rebecca Foulger Source Wessex and West Midlands GLH was added to NTRK2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NSDHL	Rebecca Foulger Source Wessex and West Midlands GLH was added to NSDHL.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NSD1	Rebecca Foulger Source Wessex and West Midlands GLH was added to NSD1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NRXN1	Rebecca Foulger Source Wessex and West Midlands GLH was added to NRXN1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NPRL3	Rebecca Foulger Source Wessex and West Midlands GLH was added to NPRL3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NHLRC1	Rebecca Foulger Source Wessex and West Midlands GLH was added to NHLRC1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NGLY1	Rebecca Foulger Source Wessex and West Midlands GLH was added to NGLY1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NDUFV1	Rebecca Foulger Source Wessex and West Midlands GLH was added to NDUFV1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NDUFS8	Rebecca Foulger Source Wessex and West Midlands GLH was added to NDUFS8.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NDUFS4	Rebecca Foulger Source Wessex and West Midlands GLH was added to NDUFS4.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NDUFAF5	Rebecca Foulger Source Wessex and West Midlands GLH was added to NDUFAF5.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NDUFAF2	Rebecca Foulger Source Wessex and West Midlands GLH was added to NDUFAF2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NDUFA10	Rebecca Foulger Source Wessex and West Midlands GLH was added to NDUFA10.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NDUFA1	Rebecca Foulger Source Wessex and West Midlands GLH was added to NDUFA1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NDE1	Rebecca Foulger Source Wessex and West Midlands GLH was added to NDE1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NARS2	Rebecca Foulger Source Wessex and West Midlands GLH was added to NARS2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NAGA	Rebecca Foulger Source Wessex and West Midlands GLH was added to NAGA.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MTR	Rebecca Foulger Source Wessex and West Midlands GLH was added to MTR.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MTHFR	Rebecca Foulger Source Wessex and West Midlands GLH was added to MTHFR.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MPDU1	Rebecca Foulger Source Wessex and West Midlands GLH was added to MPDU1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MOCS2	Rebecca Foulger Source Wessex and West Midlands GLH was added to MOCS2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MOCS1	Rebecca Foulger Source Wessex and West Midlands GLH was added to MOCS1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MMADHC	Rebecca Foulger Source Wessex and West Midlands GLH was added to MMADHC.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MMACHC	Rebecca Foulger Source Wessex and West Midlands GLH was added to MMACHC.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MLC1	Rebecca Foulger Source Wessex and West Midlands GLH was added to MLC1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MFSD8	Rebecca Foulger Source Wessex and West Midlands GLH was added to MFSD8.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MED12	Rebecca Foulger Source Wessex and West Midlands GLH was added to MED12.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MAP2K2	Rebecca Foulger Source Wessex and West Midlands GLH was added to MAP2K2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MAP2K1	Rebecca Foulger Source Wessex and West Midlands GLH was added to MAP2K1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MAGI2	Rebecca Foulger Source Wessex and West Midlands GLH was added to MAGI2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MAF	Rebecca Foulger Source Wessex and West Midlands GLH was added to MAF.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MACF1	Rebecca Foulger Source Wessex and West Midlands GLH was added to MACF1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	LYST	Rebecca Foulger Source Wessex and West Midlands GLH was added to LYST.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	LIAS	Rebecca Foulger Source Wessex and West Midlands GLH was added to LIAS.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KRAS	Rebecca Foulger Source Wessex and West Midlands GLH was added to KRAS.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KIF5C	Rebecca Foulger Source Wessex and West Midlands GLH was added to KIF5C.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KIF2A	Rebecca Foulger Source Wessex and West Midlands GLH was added to KIF2A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KIF1A	Rebecca Foulger Source Wessex and West Midlands GLH was added to KIF1A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KCTD3	Rebecca Foulger Source Wessex and West Midlands GLH was added to KCTD3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KCNQ5	Rebecca Foulger Source Wessex and West Midlands GLH was added to KCNQ5.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KCNK4	Rebecca Foulger Source Wessex and West Midlands GLH was added to KCNK4.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KCNJ11	Rebecca Foulger Source Wessex and West Midlands GLH was added to KCNJ11.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KCNA1	Rebecca Foulger Source Wessex and West Midlands GLH was added to KCNA1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KARS	Rebecca Foulger Source Wessex and West Midlands GLH was added to KARS.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	IRF2BPL	Rebecca Foulger Source Wessex and West Midlands GLH was added to IRF2BPL.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	IKBKG	Rebecca Foulger Source Wessex and West Midlands GLH was added to IKBKG.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	IFIH1	Rebecca Foulger Source Wessex and West Midlands GLH was added to IFIH1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	HSD17B4	Rebecca Foulger Source Wessex and West Midlands GLH was added to HSD17B4.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	HRAS	Rebecca Foulger Source Wessex and West Midlands GLH was added to HRAS.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	HLCS	Rebecca Foulger Source Wessex and West Midlands GLH was added to HLCS.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	HEXA	Rebecca Foulger Source Wessex and West Midlands GLH was added to HEXA.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	HEPACAM	Rebecca Foulger Source Wessex and West Midlands GLH was added to HEPACAM.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	HCN2	Rebecca Foulger Source Wessex and West Midlands GLH was added to HCN2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	HCFC1	Rebecca Foulger Source Wessex and West Midlands GLH was added to HCFC1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	HAX1	Rebecca Foulger Source Wessex and West Midlands GLH was added to HAX1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	HACE1	Rebecca Foulger Source Wessex and West Midlands GLH was added to HACE1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GTPBP2	Rebecca Foulger Source Wessex and West Midlands GLH was added to GTPBP2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GRIN2D	Rebecca Foulger Source Wessex and West Midlands GLH was added to GRIN2D.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GRIA4	Rebecca Foulger Source Wessex and West Midlands GLH was added to GRIA4.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GPHN	Rebecca Foulger Source Wessex and West Midlands GLH was added to GPHN.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GOSR2	Rebecca Foulger Source Wessex and West Midlands GLH was added to GOSR2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GNB5	Rebecca Foulger Source Wessex and West Midlands GLH was added to GNB5.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GNB1	Rebecca Foulger Source Wessex and West Midlands GLH was added to GNB1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GNAQ	Rebecca Foulger Source Wessex and West Midlands GLH was added to GNAQ.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GM2A	Rebecca Foulger Source Wessex and West Midlands GLH was added to GM2A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GLUL	Rebecca Foulger Source Wessex and West Midlands GLH was added to GLUL.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GLUD1	Rebecca Foulger Source Wessex and West Midlands GLH was added to GLUD1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GLDC	Rebecca Foulger Source Wessex and West Midlands GLH was added to GLDC.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GLB1	Rebecca Foulger Source Wessex and West Midlands GLH was added to GLB1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GFM1	Rebecca Foulger Source Wessex and West Midlands GLH was added to GFM1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GFAP	Rebecca Foulger Source Wessex and West Midlands GLH was added to GFAP.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GCH1	Rebecca Foulger Source Wessex and West Midlands GLH was added to GCH1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GBA	Rebecca Foulger Source Wessex and West Midlands GLH was added to GBA.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GAMT	Rebecca Foulger Source Wessex and West Midlands GLH was added to GAMT.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GALC	Rebecca Foulger Source Wessex and West Midlands GLH was added to GALC.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GABRB2	Rebecca Foulger Source Wessex and West Midlands GLH was added to GABRB2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	FUT8	Rebecca Foulger Source Wessex and West Midlands GLH was added to FUT8.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	FUCA1	Rebecca Foulger Source Wessex and West Midlands GLH was added to FUCA1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	FRRS1L	Rebecca Foulger Source Wessex and West Midlands GLH was added to FRRS1L.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	FOLR1	Rebecca Foulger Source Wessex and West Midlands GLH was added to FOLR1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	FLNA	Rebecca Foulger Source Wessex and West Midlands GLH was added to FLNA.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	FKTN	Rebecca Foulger Source Wessex and West Midlands GLH was added to FKTN.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	FH	Rebecca Foulger Source Wessex and West Midlands GLH was added to FH.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	FGFR3	Rebecca Foulger Source Wessex and West Midlands GLH was added to FGFR3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	FGF12	Rebecca Foulger Source Wessex and West Midlands GLH was added to FGF12.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	FBXO11	Rebecca Foulger Source Wessex and West Midlands GLH was added to FBXO11.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	FBXL4	Rebecca Foulger Source Wessex and West Midlands GLH was added to FBXL4.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	FARS2	Rebecca Foulger Source Wessex and West Midlands GLH was added to FARS2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	FAR1	Rebecca Foulger Source Wessex and West Midlands GLH was added to FAR1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	EXOSC3	Rebecca Foulger Source Wessex and West Midlands GLH was added to EXOSC3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ETHE1	Rebecca Foulger Source Wessex and West Midlands GLH was added to ETHE1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	EMX2	Rebecca Foulger Source Wessex and West Midlands GLH was added to EMX2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	EIF3F	Rebecca Foulger Source Wessex and West Midlands GLH was added to EIF3F.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	EIF2S3	Rebecca Foulger Source Wessex and West Midlands GLH was added to EIF2S3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	EIF2B5	Rebecca Foulger Source Wessex and West Midlands GLH was added to EIF2B5.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	EIF2B4	Rebecca Foulger Source Wessex and West Midlands GLH was added to EIF2B4.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	EIF2B2	Rebecca Foulger Source Wessex and West Midlands GLH was added to EIF2B2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	EFTUD2	Rebecca Foulger Source Wessex and West Midlands GLH was added to EFTUD2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	EEF1A2	Rebecca Foulger Source Wessex and West Midlands GLH was added to EEF1A2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	EARS2	Rebecca Foulger Source Wessex and West Midlands GLH was added to EARS2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DYNC1H1	Rebecca Foulger Source Wessex and West Midlands GLH was added to DYNC1H1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DPM1	Rebecca Foulger Source Wessex and West Midlands GLH was added to DPM1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DPAGT1	Rebecca Foulger Source Wessex and West Midlands GLH was added to DPAGT1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DNM1L	Rebecca Foulger Source Wessex and West Midlands GLH was added to DNM1L.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DHX30	Rebecca Foulger Source Wessex and West Midlands GLH was added to DHX30.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DHDDS	Rebecca Foulger Source Wessex and West Midlands GLH was added to DHDDS.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DHCR7	Rebecca Foulger Source Wessex and West Midlands GLH was added to DHCR7.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DENND5A	Rebecca Foulger Source Wessex and West Midlands GLH was added to DENND5A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DEAF1	Rebecca Foulger Source Wessex and West Midlands GLH was added to DEAF1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DDX3X	Rebecca Foulger Source Wessex and West Midlands GLH was added to DDX3X.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DCX	Rebecca Foulger Source Wessex and West Midlands GLH was added to DCX.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	D2HGDH	Rebecca Foulger Source Wessex and West Midlands GLH was added to D2HGDH.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CTSD	Rebecca Foulger Source Wessex and West Midlands GLH was added to CTSD.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CSTB	Rebecca Foulger Source Wessex and West Midlands GLH was added to CSTB.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CREBBP	Rebecca Foulger Source Wessex and West Midlands GLH was added to CREBBP.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	COQ9	Rebecca Foulger Source Wessex and West Midlands GLH was added to COQ9.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	COQ4	Rebecca Foulger Source Wessex and West Midlands GLH was added to COQ4.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	COQ2	Rebecca Foulger Source Wessex and West Midlands GLH was added to COQ2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	COL4A2	Rebecca Foulger Source Wessex and West Midlands GLH was added to COL4A2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	COL4A1	Rebecca Foulger Source Wessex and West Midlands GLH was added to COL4A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	COL18A1	Rebecca Foulger Source Wessex and West Midlands GLH was added to COL18A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	COG7	Rebecca Foulger Source Wessex and West Midlands GLH was added to COG7.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CNNM2	Rebecca Foulger Source Wessex and West Midlands GLH was added to CNNM2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CLN3	Rebecca Foulger Source Wessex and West Midlands GLH was added to CLN3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CLCN4	Rebecca Foulger Source Wessex and West Midlands GLH was added to CLCN4.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CC2D2A	Rebecca Foulger Source Wessex and West Midlands GLH was added to CC2D2A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CASK	Rebecca Foulger Source Wessex and West Midlands GLH was added to CASK.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CAD	Rebecca Foulger Source Wessex and West Midlands GLH was added to CAD.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CACNA1G	Rebecca Foulger Source Wessex and West Midlands GLH was added to CACNA1G.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CACNA1E	Rebecca Foulger Source Wessex and West Midlands GLH was added to CACNA1E.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CACNA1A	Rebecca Foulger Source Wessex and West Midlands GLH was added to CACNA1A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	C12orf57	Rebecca Foulger Source Wessex and West Midlands GLH was added to C12orf57.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	BTD	Rebecca Foulger Source Wessex and West Midlands GLH was added to BTD.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	BRAF	Rebecca Foulger Source Wessex and West Midlands GLH was added to BRAF.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	BOLA3	Rebecca Foulger Source Wessex and West Midlands GLH was added to BOLA3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	BCS1L	Rebecca Foulger Source Wessex and West Midlands GLH was added to BCS1L.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	BCKDHB	Rebecca Foulger Source Wessex and West Midlands GLH was added to BCKDHB.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	BCKDHA	Rebecca Foulger Source Wessex and West Midlands GLH was added to BCKDHA.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ATP7A	Rebecca Foulger Source Wessex and West Midlands GLH was added to ATP7A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ATP6V1A	Rebecca Foulger Source Wessex and West Midlands GLH was added to ATP6V1A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ATP1A1	Rebecca Foulger Source Wessex and West Midlands GLH was added to ATP1A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ASPA	Rebecca Foulger Source Wessex and West Midlands GLH was added to ASPA.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ARV1	Rebecca Foulger Source Wessex and West Midlands GLH was added to ARV1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ARID1B	Rebecca Foulger Source Wessex and West Midlands GLH was added to ARID1B.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ARG1	Rebecca Foulger Source Wessex and West Midlands GLH was added to ARG1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ARFGEF2	Rebecca Foulger Source Wessex and West Midlands GLH was added to ARFGEF2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	AP3B2	Rebecca Foulger Source Wessex and West Midlands GLH was added to AP3B2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	AMT	Rebecca Foulger Source Wessex and West Midlands GLH was added to AMT.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	AMPD2	Rebecca Foulger Source Wessex and West Midlands GLH was added to AMPD2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ALPL	Rebecca Foulger Source Wessex and West Midlands GLH was added to ALPL.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ALG9	Rebecca Foulger Source Wessex and West Midlands GLH was added to ALG9.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ALG8	Rebecca Foulger Source Wessex and West Midlands GLH was added to ALG8.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ALG6	Rebecca Foulger Source Wessex and West Midlands GLH was added to ALG6.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ALG3	Rebecca Foulger Source Wessex and West Midlands GLH was added to ALG3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ALG1	Rebecca Foulger Source Wessex and West Midlands GLH was added to ALG1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ALDH5A1	Rebecca Foulger Source Wessex and West Midlands GLH was added to ALDH5A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	AKT3	Rebecca Foulger Source Wessex and West Midlands GLH was added to AKT3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	AKT1	Rebecca Foulger Source Wessex and West Midlands GLH was added to AKT1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	AIMP1	Rebecca Foulger Source Wessex and West Midlands GLH was added to AIMP1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ADPRHL2	Rebecca Foulger Source Wessex and West Midlands GLH was added to ADPRHL2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ADGRG1	Rebecca Foulger Source Wessex and West Midlands GLH was added to ADGRG1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ADAR	Rebecca Foulger Source Wessex and West Midlands GLH was added to ADAR.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ACOX1	Rebecca Foulger Source Wessex and West Midlands GLH was added to ACOX1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ABAT	Rebecca Foulger Source Wessex and West Midlands GLH was added to ABAT.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ZEB2	Rebecca Foulger Source Wessex and West Midlands GLH was added to ZEB2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	WWOX	Rebecca Foulger Source Wessex and West Midlands GLH was added to WWOX.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	WDR45B	Rebecca Foulger Source Wessex and West Midlands GLH was added to WDR45B.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	WDR45	Rebecca Foulger Source Wessex and West Midlands GLH was added to WDR45.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	UBE3A	Rebecca Foulger Source Wessex and West Midlands GLH was added to UBE3A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	UBE2A	Rebecca Foulger Source Wessex and West Midlands GLH was added to UBE2A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TRPM6	Rebecca Foulger Source Wessex and West Midlands GLH was added to TRPM6.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TRAK1	Rebecca Foulger Source Wessex and West Midlands GLH was added to TRAK1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TPP1	Rebecca Foulger Source Wessex and West Midlands GLH was added to TPP1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TCF4	Rebecca Foulger Source Wessex and West Midlands GLH was added to TCF4.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	TBC1D24	Rebecca Foulger Source Wessex and West Midlands GLH was added to TBC1D24.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SZT2	Rebecca Foulger Source Wessex and West Midlands GLH was added to SZT2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SYNJ1	Rebecca Foulger Source Wessex and West Midlands GLH was added to SYNJ1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SYNGAP1	Rebecca Foulger Source Wessex and West Midlands GLH was added to SYNGAP1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SUOX	Rebecca Foulger Source Wessex and West Midlands GLH was added to SUOX.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	STXBP1	Rebecca Foulger Source Wessex and West Midlands GLH was added to STXBP1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	STX1B	Rebecca Foulger Source Wessex and West Midlands GLH was added to STX1B.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	STRADA	Rebecca Foulger Source Wessex and West Midlands GLH was added to STRADA.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SPTAN1	Rebecca Foulger Source Wessex and West Midlands GLH was added to SPTAN1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SLC9A6	Rebecca Foulger Source Wessex and West Midlands GLH was added to SLC9A6.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SLC6A19	Rebecca Foulger Source Wessex and West Midlands GLH was added to SLC6A19.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SLC6A1	Rebecca Foulger Source Wessex and West Midlands GLH was added to SLC6A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SLC35A2	Rebecca Foulger Source Wessex and West Midlands GLH was added to SLC35A2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SLC2A1	Rebecca Foulger Source Wessex and West Midlands GLH was added to SLC2A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SLC25A22	Rebecca Foulger Source Wessex and West Midlands GLH was added to SLC25A22.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SLC25A1	Rebecca Foulger Source Wessex and West Midlands GLH was added to SLC25A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SLC1A2	Rebecca Foulger Source Wessex and West Midlands GLH was added to SLC1A2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SLC16A2	Rebecca Foulger Source Wessex and West Midlands GLH was added to SLC16A2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SLC13A5	Rebecca Foulger Source Wessex and West Midlands GLH was added to SLC13A5.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SLC12A5	Rebecca Foulger Source Wessex and West Midlands GLH was added to SLC12A5.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SIK1	Rebecca Foulger Source Wessex and West Midlands GLH was added to SIK1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SETD5	Rebecca Foulger Source Wessex and West Midlands GLH was added to SETD5.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SCN9A	Rebecca Foulger Source Wessex and West Midlands GLH was added to SCN9A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SCN8A	Rebecca Foulger Source Wessex and West Midlands GLH was added to SCN8A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SCN2A	Rebecca Foulger Source Wessex and West Midlands GLH was added to SCN2A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SCN1B	Rebecca Foulger Source Wessex and West Midlands GLH was added to SCN1B.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SCN1A	Rebecca Foulger Source Wessex and West Midlands GLH was added to SCN1A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	SCARB2	Rebecca Foulger Source Wessex and West Midlands GLH was added to SCARB2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	RANBP2	Rebecca Foulger Source Wessex and West Midlands GLH was added to RANBP2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	QARS	Rebecca Foulger Source Wessex and West Midlands GLH was added to QARS.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PURA	Rebecca Foulger Source Wessex and West Midlands GLH was added to PURA.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PRRT2	Rebecca Foulger Source Wessex and West Midlands GLH was added to PRRT2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PRODH	Rebecca Foulger Source Wessex and West Midlands GLH was added to PRODH.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	POLG	Rebecca Foulger Source Wessex and West Midlands GLH was added to POLG.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PNPO	Rebecca Foulger Source Wessex and West Midlands GLH was added to PNPO.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PNKP	Rebecca Foulger Source Wessex and West Midlands GLH was added to PNKP.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PLPBP	Rebecca Foulger Source Wessex and West Midlands GLH was added to PLPBP.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PLCB1	Rebecca Foulger Source Wessex and West Midlands GLH was added to PLCB1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PIGT	Rebecca Foulger Source Wessex and West Midlands GLH was added to PIGT.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PIGN	Rebecca Foulger Source Wessex and West Midlands GLH was added to PIGN.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PIGA	Rebecca Foulger Source Wessex and West Midlands GLH was added to PIGA.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	PCDH19	Rebecca Foulger Source Wessex and West Midlands GLH was added to PCDH19.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NEXMIF	Rebecca Foulger Source Wessex and West Midlands GLH was added to NEXMIF.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	NACC1	Rebecca Foulger Source Wessex and West Midlands GLH was added to NACC1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MTOR	Rebecca Foulger Source Wessex and West Midlands GLH was added to MTOR.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MOGS	Rebecca Foulger Source Wessex and West Midlands GLH was added to MOGS.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MFF	Rebecca Foulger Source Wessex and West Midlands GLH was added to MFF.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MEF2C	Rebecca Foulger Source Wessex and West Midlands GLH was added to MEF2C.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MECP2	Rebecca Foulger Source Wessex and West Midlands GLH was added to MECP2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MDH2	Rebecca Foulger Source Wessex and West Midlands GLH was added to MDH2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MBOAT7	Rebecca Foulger Source Wessex and West Midlands GLH was added to MBOAT7.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	MBD5	Rebecca Foulger Source Wessex and West Midlands GLH was added to MBD5.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	LGI1	Rebecca Foulger Source Wessex and West Midlands GLH was added to LGI1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KIF1BP	Rebecca Foulger Source Wessex and West Midlands GLH was added to KIF1BP.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KCTD7	Rebecca Foulger Source Wessex and West Midlands GLH was added to KCTD7.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KCNT1	Rebecca Foulger Source Wessex and West Midlands GLH was added to KCNT1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KCNQ3	Rebecca Foulger Source Wessex and West Midlands GLH was added to KCNQ3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KCNQ2	Rebecca Foulger Source Wessex and West Midlands GLH was added to KCNQ2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KCNJ10	Rebecca Foulger Source Wessex and West Midlands GLH was added to KCNJ10.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KCNC1	Rebecca Foulger Source Wessex and West Midlands GLH was added to KCNC1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KCNB1	Rebecca Foulger Source Wessex and West Midlands GLH was added to KCNB1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	KCNA2	Rebecca Foulger Source Wessex and West Midlands GLH was added to KCNA2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ITPA	Rebecca Foulger Source Wessex and West Midlands GLH was added to ITPA.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	IQSEC2	Rebecca Foulger Source Wessex and West Midlands GLH was added to IQSEC2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	IER3IP1	Rebecca Foulger Source Wessex and West Midlands GLH was added to IER3IP1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	IDH2	Rebecca Foulger Source Wessex and West Midlands GLH was added to IDH2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	HTRA2	Rebecca Foulger Source Wessex and West Midlands GLH was added to HTRA2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	HNRNPU	Rebecca Foulger Source Wessex and West Midlands GLH was added to HNRNPU.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	HNRNPH2	Rebecca Foulger Source Wessex and West Midlands GLH was added to HNRNPH2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	HMGCL	Rebecca Foulger Source Wessex and West Midlands GLH was added to HMGCL.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	HECW2	Rebecca Foulger Source Wessex and West Midlands GLH was added to HECW2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	HCN1	Rebecca Foulger Source Wessex and West Midlands GLH was added to HCN1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GSS	Rebecca Foulger Source Wessex and West Midlands GLH was added to GSS.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GRIN2B	Rebecca Foulger Source Wessex and West Midlands GLH was added to GRIN2B.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GRIN2A	Rebecca Foulger Source Wessex and West Midlands GLH was added to GRIN2A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GRIN1	Rebecca Foulger Source Wessex and West Midlands GLH was added to GRIN1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GPAA1	Rebecca Foulger Source Wessex and West Midlands GLH was added to GPAA1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GNAO1	Rebecca Foulger Source Wessex and West Midlands GLH was added to GNAO1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GLYCTK	Rebecca Foulger Source Wessex and West Midlands GLH was added to GLYCTK.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GABRG2	Rebecca Foulger Source Wessex and West Midlands GLH was added to GABRG2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GABRB3	Rebecca Foulger Source Wessex and West Midlands GLH was added to GABRB3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GABRA1	Rebecca Foulger Source Wessex and West Midlands GLH was added to GABRA1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	GABBR2	Rebecca Foulger Source Wessex and West Midlands GLH was added to GABBR2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	FOXG1	Rebecca Foulger Source Wessex and West Midlands GLH was added to FOXG1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	EPM2A	Rebecca Foulger Source Wessex and West Midlands GLH was added to EPM2A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	EPG5	Rebecca Foulger Source Wessex and West Midlands GLH was added to EPG5.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	EML1	Rebecca Foulger Source Wessex and West Midlands GLH was added to EML1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	EHMT1	Rebecca Foulger Source Wessex and West Midlands GLH was added to EHMT1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DYRK1A	Rebecca Foulger Source Wessex and West Midlands GLH was added to DYRK1A.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DPYD	Rebecca Foulger Source Wessex and West Midlands GLH was added to DPYD.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DOCK7	Rebecca Foulger Source Wessex and West Midlands GLH was added to DOCK7.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DNM1	Rebecca Foulger Source Wessex and West Midlands GLH was added to DNM1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DIAPH1	Rebecca Foulger Source Wessex and West Midlands GLH was added to DIAPH1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	DEPDC5	Rebecca Foulger Source Wessex and West Midlands GLH was added to DEPDC5.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CYFIP2	Rebecca Foulger Source Wessex and West Midlands GLH was added to CYFIP2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CPA6	Rebecca Foulger Source Wessex and West Midlands GLH was added to CPA6.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CNTNAP2	Rebecca Foulger Source Wessex and West Midlands GLH was added to CNTNAP2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CNKSR2	Rebecca Foulger Source Wessex and West Midlands GLH was added to CNKSR2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CLTC	Rebecca Foulger Source Wessex and West Midlands GLH was added to CLTC.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CLN8	Rebecca Foulger Source Wessex and West Midlands GLH was added to CLN8.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CIC	Rebecca Foulger Source Wessex and West Midlands GLH was added to CIC.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CHRNB2	Rebecca Foulger Source Wessex and West Midlands GLH was added to CHRNB2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CHRNA4	Rebecca Foulger Source Wessex and West Midlands GLH was added to CHRNA4.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CHRNA2	Rebecca Foulger Source Wessex and West Midlands GLH was added to CHRNA2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CHD2	Rebecca Foulger Source Wessex and West Midlands GLH was added to CHD2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CDKL5	Rebecca Foulger Source Wessex and West Midlands GLH was added to CDKL5.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	CACNA1D	Rebecca Foulger Source Wessex and West Midlands GLH was added to CACNA1D.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	BSCL2	Rebecca Foulger Source Wessex and West Midlands GLH was added to BSCL2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	BRAT1	Rebecca Foulger Source Wessex and West Midlands GLH was added to BRAT1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ATRX	Rebecca Foulger Source Wessex and West Midlands GLH was added to ATRX.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ATP6V0A2	Rebecca Foulger Source Wessex and West Midlands GLH was added to ATP6V0A2.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ATP1A3	Rebecca Foulger Source Wessex and West Midlands GLH was added to ATP1A3.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ARX	Rebecca Foulger Source Wessex and West Midlands GLH was added to ARX.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ARHGEF9	Rebecca Foulger Source Wessex and West Midlands GLH was added to ARHGEF9.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ALG13	Rebecca Foulger Source Wessex and West Midlands GLH was added to ALG13.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ALG11	Rebecca Foulger Source Wessex and West Midlands GLH was added to ALG11.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ALDH7A1	Rebecca Foulger Source Wessex and West Midlands GLH was added to ALDH7A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	ADSL	Rebecca Foulger Source Wessex and West Midlands GLH was added to ADSL.
06 Aug 2019	Early onset or syndromic epilepsy v1.191	AARS	Rebecca Foulger Source Wessex and West Midlands GLH was added to AARS.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TUBA3E	Rebecca Foulger Source NHS GMS was added to TUBA3E.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SLC6A5	Rebecca Foulger Source NHS GMS was added to SLC6A5.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SHH	Rebecca Foulger Source NHS GMS was added to SHH.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SEC24D	Rebecca Foulger Source NHS GMS was added to SEC24D.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SCN2B	Rebecca Foulger Source NHS GMS was added to SCN2B.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RYR3	Rebecca Foulger Source NHS GMS was added to RYR3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RUBCN	Rebecca Foulger Source NHS GMS was added to RUBCN.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PSMB8	Rebecca Foulger Source NHS GMS was added to PSMB8.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PRICKLE2	Rebecca Foulger Source NHS GMS was added to PRICKLE2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PCDHB4	Rebecca Foulger Source NHS GMS was added to PCDHB4.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NRAS	Rebecca Foulger Source NHS GMS was added to NRAS.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NID1	Rebecca Foulger Source NHS GMS was added to NID1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NDUFA11	Rebecca Foulger Source NHS GMS was added to NDUFA11.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MT-TL1	Rebecca Foulger Source NHS GMS was added to MT-TL1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MATN4	Rebecca Foulger Source NHS GMS was added to MATN4.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MAPK10	Rebecca Foulger Source NHS GMS was added to MAPK10.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KAT5	Rebecca Foulger Source NHS GMS was added to KAT5.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	INO80	Rebecca Foulger Source NHS GMS was added to INO80.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	H3F3B	Rebecca Foulger Source NHS GMS was added to H3F3B.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	H3F3A	Rebecca Foulger Source NHS GMS was added to H3F3A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GLRB	Rebecca Foulger Source NHS GMS was added to GLRB.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GCSH	Rebecca Foulger Source NHS GMS was added to GCSH.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GATM	Rebecca Foulger Source NHS GMS was added to GATM.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GATAD2B	Rebecca Foulger Source NHS GMS was added to GATAD2B.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GAL	Rebecca Foulger Source NHS GMS was added to GAL.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GABRD	Rebecca Foulger Source NHS GMS was added to GABRD.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	FTL	Rebecca Foulger Source NHS GMS was added to FTL.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	FIG4	Rebecca Foulger Source NHS GMS was added to FIG4.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DMBX1	Rebecca Foulger Source NHS GMS was added to DMBX1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CYP27A1	Rebecca Foulger Source NHS GMS was added to CYP27A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CSNK1G1	Rebecca Foulger Source NHS GMS was added to CSNK1G1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CRH	Rebecca Foulger Source NHS GMS was added to CRH.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CNTN2	Rebecca Foulger Source NHS GMS was added to CNTN2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CLN6	Rebecca Foulger Source NHS GMS was added to CLN6.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CLN5	Rebecca Foulger Source NHS GMS was added to CLN5.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CLCN2	Rebecca Foulger Source NHS GMS was added to CLCN2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CBL	Rebecca Foulger Source NHS GMS was added to CBL.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CASR	Rebecca Foulger Source NHS GMS was added to CASR.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CAMK2G	Rebecca Foulger Source NHS GMS was added to CAMK2G.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CACNB4	Rebecca Foulger Source NHS GMS was added to CACNB4.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ASAH1	Rebecca Foulger Source NHS GMS was added to ASAH1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ALG2	Rebecca Foulger Source NHS GMS was added to ALG2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ALG12	Rebecca Foulger Source NHS GMS was added to ALG12.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ADGRV1	Rebecca Foulger Source NHS GMS was added to ADGRV1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	AARS2	Rebecca Foulger Source NHS GMS was added to AARS2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	VLDLR	Rebecca Foulger Source NHS GMS was added to VLDLR.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	UFC1	Rebecca Foulger Source NHS GMS was added to UFC1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TXNRD1	Rebecca Foulger Source NHS GMS was added to TXNRD1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TUBB	Rebecca Foulger Source NHS GMS was added to TUBB.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TUBA8	Rebecca Foulger Source NHS GMS was added to TUBA8.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TSFM	Rebecca Foulger Source NHS GMS was added to TSFM.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TSEN34	Rebecca Foulger Source NHS GMS was added to TSEN34.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TSEN15	Rebecca Foulger Source NHS GMS was added to TSEN15.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TRIP13	Rebecca Foulger Source NHS GMS was added to TRIP13.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TRAPPC6B	Rebecca Foulger Source NHS GMS was added to TRAPPC6B.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TRAPPC12	Rebecca Foulger Source NHS GMS was added to TRAPPC12.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TRAF7	Rebecca Foulger Source NHS GMS was added to TRAF7.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TNK2	Rebecca Foulger Source NHS GMS was added to TNK2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TIMM50	Rebecca Foulger Source NHS GMS was added to TIMM50.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TFE3	Rebecca Foulger Source NHS GMS was added to TFE3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TELO2	Rebecca Foulger Source NHS GMS was added to TELO2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TBC1D20	Rebecca Foulger Source NHS GMS was added to TBC1D20.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SUCLG1	Rebecca Foulger Source NHS GMS was added to SUCLG1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ST3GAL3	Rebecca Foulger Source NHS GMS was added to ST3GAL3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SRPX2	Rebecca Foulger Source NHS GMS was added to SRPX2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SPR	Rebecca Foulger Source NHS GMS was added to SPR.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SNIP1	Rebecca Foulger Source NHS GMS was added to SNIP1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SMC1A	Rebecca Foulger Source NHS GMS was added to SMC1A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SLC45A1	Rebecca Foulger Source NHS GMS was added to SLC45A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SLC35A1	Rebecca Foulger Source NHS GMS was added to SLC35A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SIX3	Rebecca Foulger Source NHS GMS was added to SIX3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SETD1B	Rebecca Foulger Source NHS GMS was added to SETD1B.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SDHA	Rebecca Foulger Source NHS GMS was added to SDHA.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RYR2	Rebecca Foulger Source NHS GMS was added to RYR2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RUSC2	Rebecca Foulger Source NHS GMS was added to RUSC2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RRM2B	Rebecca Foulger Source NHS GMS was added to RRM2B.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RPIA	Rebecca Foulger Source NHS GMS was added to RPIA.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RNU4ATAC	Rebecca Foulger Source NHS GMS was added to RNU4ATAC.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RAB3GAP2	Rebecca Foulger Source NHS GMS was added to RAB3GAP2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RAB3GAP1	Rebecca Foulger Source NHS GMS was added to RAB3GAP1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PTF1A	Rebecca Foulger Source NHS GMS was added to PTF1A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PSPH	Rebecca Foulger Source NHS GMS was added to PSPH.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PSAT1	Rebecca Foulger Source NHS GMS was added to PSAT1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	POMT2	Rebecca Foulger Source NHS GMS was added to POMT2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PIGQ	Rebecca Foulger Source NHS GMS was added to PIGQ.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PIGH	Rebecca Foulger Source NHS GMS was added to PIGH.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PIGC	Rebecca Foulger Source NHS GMS was added to PIGC.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PEX5	Rebecca Foulger Source NHS GMS was added to PEX5.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PDSS2	Rebecca Foulger Source NHS GMS was added to PDSS2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PCLO	Rebecca Foulger Source NHS GMS was added to PCLO.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	OTX2	Rebecca Foulger Source NHS GMS was added to OTX2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NUBPL	Rebecca Foulger Source NHS GMS was added to NUBPL.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NPRL2	Rebecca Foulger Source NHS GMS was added to NPRL2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NEDD4L	Rebecca Foulger Source NHS GMS was added to NEDD4L.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NECAP1	Rebecca Foulger Source NHS GMS was added to NECAP1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NDUFS7	Rebecca Foulger Source NHS GMS was added to NDUFS7.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NDUFS6	Rebecca Foulger Source NHS GMS was added to NDUFS6.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NDUFS2	Rebecca Foulger Source NHS GMS was added to NDUFS2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NDUFS1	Rebecca Foulger Source NHS GMS was added to NDUFS1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NDUFAF4	Rebecca Foulger Source NHS GMS was added to NDUFAF4.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NDUFAF3	Rebecca Foulger Source NHS GMS was added to NDUFAF3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NDUFA2	Rebecca Foulger Source NHS GMS was added to NDUFA2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NDP	Rebecca Foulger Source NHS GMS was added to NDP.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MED17	Rebecca Foulger Source NHS GMS was added to MED17.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MAST1	Rebecca Foulger Source NHS GMS was added to MAST1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MANBA	Rebecca Foulger Source NHS GMS was added to MANBA.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	LNPK	Rebecca Foulger Source NHS GMS was added to LNPK.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	LIPT2	Rebecca Foulger Source NHS GMS was added to LIPT2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	LARGE1	Rebecca Foulger Source NHS GMS was added to LARGE1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KPTN	Rebecca Foulger Source NHS GMS was added to KPTN.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KIAA1109	Rebecca Foulger Source NHS GMS was added to KIAA1109.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KCNMA1	Rebecca Foulger Source NHS GMS was added to KCNMA1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ISPD	Rebecca Foulger Source NHS GMS was added to ISPD.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	HSPD1	Rebecca Foulger Source NHS GMS was added to HSPD1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	HPRT1	Rebecca Foulger Source NHS GMS was added to HPRT1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	HOXA1	Rebecca Foulger Source NHS GMS was added to HOXA1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	HEXB	Rebecca Foulger Source NHS GMS was added to HEXB.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	HCCS	Rebecca Foulger Source NHS GMS was added to HCCS.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GTPBP3	Rebecca Foulger Source NHS GMS was added to GTPBP3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GLRA1	Rebecca Foulger Source NHS GMS was added to GLRA1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GLI3	Rebecca Foulger Source NHS GMS was added to GLI3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	FOXRED1	Rebecca Foulger Source NHS GMS was added to FOXRED1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	FKRP	Rebecca Foulger Source NHS GMS was added to FKRP.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	FASTKD2	Rebecca Foulger Source NHS GMS was added to FASTKD2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	EIF2B3	Rebecca Foulger Source NHS GMS was added to EIF2B3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	EIF2B1	Rebecca Foulger Source NHS GMS was added to EIF2B1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	EFHC1	Rebecca Foulger Source NHS GMS was added to EFHC1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DPM2	Rebecca Foulger Source NHS GMS was added to DPM2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DOLK	Rebecca Foulger Source NHS GMS was added to DOLK.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DNAJC6	Rebecca Foulger Source NHS GMS was added to DNAJC6.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DHCR24	Rebecca Foulger Source NHS GMS was added to DHCR24.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DBT	Rebecca Foulger Source NHS GMS was added to DBT.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CUX2	Rebecca Foulger Source NHS GMS was added to CUX2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CSNK2B	Rebecca Foulger Source NHS GMS was added to CSNK2B.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	COX15	Rebecca Foulger Source NHS GMS was added to COX15.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	COX10	Rebecca Foulger Source NHS GMS was added to COX10.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	COQ6	Rebecca Foulger Source NHS GMS was added to COQ6.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	COG8	Rebecca Foulger Source NHS GMS was added to COG8.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	COG6	Rebecca Foulger Source NHS GMS was added to COG6.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	COG4	Rebecca Foulger Source NHS GMS was added to COG4.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CNPY3	Rebecca Foulger Source NHS GMS was added to CNPY3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CCND2	Rebecca Foulger Source NHS GMS was added to CCND2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CCDC88C	Rebecca Foulger Source NHS GMS was added to CCDC88C.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CCDC88A	Rebecca Foulger Source NHS GMS was added to CCDC88A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CACNA2D2	Rebecca Foulger Source NHS GMS was added to CACNA2D2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CACNA1H	Rebecca Foulger Source NHS GMS was added to CACNA1H.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ATP6AP2	Rebecca Foulger Source NHS GMS was added to ATP6AP2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ATP5A1	Rebecca Foulger Source NHS GMS was added to ATP5A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ATP1A2	Rebecca Foulger Source NHS GMS was added to ATP1A2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ADAT3	Rebecca Foulger Source NHS GMS was added to ADAT3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ZBTB18	Rebecca Foulger Source NHS GMS was added to ZBTB18.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	YWHAG	Rebecca Foulger Source NHS GMS was added to YWHAG.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	WDR73	Rebecca Foulger Source NHS GMS was added to WDR73.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	WDR62	Rebecca Foulger Source NHS GMS was added to WDR62.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	WASF1	Rebecca Foulger Source NHS GMS was added to WASF1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	VARS	Rebecca Foulger Source NHS GMS was added to VARS.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	UNC80	Rebecca Foulger Source NHS GMS was added to UNC80.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	UFM1	Rebecca Foulger Source NHS GMS was added to UFM1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	UBA5	Rebecca Foulger Source NHS GMS was added to UBA5.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TUBG1	Rebecca Foulger Source NHS GMS was added to TUBG1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TUBB4A	Rebecca Foulger Source NHS GMS was added to TUBB4A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TUBB3	Rebecca Foulger Source NHS GMS was added to TUBB3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TUBB2B	Rebecca Foulger Source NHS GMS was added to TUBB2B.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TUBB2A	Rebecca Foulger Source NHS GMS was added to TUBB2A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TUBA1A	Rebecca Foulger Source NHS GMS was added to TUBA1A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TSEN54	Rebecca Foulger Source NHS GMS was added to TSEN54.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TSEN2	Rebecca Foulger Source NHS GMS was added to TSEN2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TSC2	Rebecca Foulger Source NHS GMS was added to TSC2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TSC1	Rebecca Foulger Source NHS GMS was added to TSC1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TRIM8	Rebecca Foulger Source NHS GMS was added to TRIM8.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TREX1	Rebecca Foulger Source NHS GMS was added to TREX1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TMEM70	Rebecca Foulger Source NHS GMS was added to TMEM70.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TBL1XR1	Rebecca Foulger Source NHS GMS was added to TBL1XR1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TBCK	Rebecca Foulger Source NHS GMS was added to TBCK.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TBCD	Rebecca Foulger Source NHS GMS was added to TBCD.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TANGO2	Rebecca Foulger Source NHS GMS was added to TANGO2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SYN1	Rebecca Foulger Source NHS GMS was added to SYN1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SURF1	Rebecca Foulger Source NHS GMS was added to SURF1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SUCLA2	Rebecca Foulger Source NHS GMS was added to SUCLA2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	STAMBP	Rebecca Foulger Source NHS GMS was added to STAMBP.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	STAG1	Rebecca Foulger Source NHS GMS was added to STAG1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ST3GAL5	Rebecca Foulger Source NHS GMS was added to ST3GAL5.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SNORD118	Rebecca Foulger Source NHS GMS was added to SNORD118.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SMS	Rebecca Foulger Source NHS GMS was added to SMS.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SMARCA2	Rebecca Foulger Source NHS GMS was added to SMARCA2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SLC6A8	Rebecca Foulger Source NHS GMS was added to SLC6A8.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SLC25A12	Rebecca Foulger Source NHS GMS was added to SLC25A12.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SLC1A4	Rebecca Foulger Source NHS GMS was added to SLC1A4.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SETBP1	Rebecca Foulger Source NHS GMS was added to SETBP1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SEPSECS	Rebecca Foulger Source NHS GMS was added to SEPSECS.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SCO2	Rebecca Foulger Source NHS GMS was added to SCO2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SCO1	Rebecca Foulger Source NHS GMS was added to SCO1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SCN3A	Rebecca Foulger Source NHS GMS was added to SCN3A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SAMHD1	Rebecca Foulger Source NHS GMS was added to SAMHD1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RTTN	Rebecca Foulger Source NHS GMS was added to RTTN.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RTN4IP1	Rebecca Foulger Source NHS GMS was added to RTN4IP1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RORB	Rebecca Foulger Source NHS GMS was added to RORB.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RORA	Rebecca Foulger Source NHS GMS was added to RORA.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ROGDI	Rebecca Foulger Source NHS GMS was added to ROGDI.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RNASET2	Rebecca Foulger Source NHS GMS was added to RNASET2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RNASEH2C	Rebecca Foulger Source NHS GMS was added to RNASEH2C.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RNASEH2B	Rebecca Foulger Source NHS GMS was added to RNASEH2B.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RNASEH2A	Rebecca Foulger Source NHS GMS was added to RNASEH2A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RMND1	Rebecca Foulger Source NHS GMS was added to RMND1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RHOBTB2	Rebecca Foulger Source NHS GMS was added to RHOBTB2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RFT1	Rebecca Foulger Source NHS GMS was added to RFT1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RELN	Rebecca Foulger Source NHS GMS was added to RELN.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RARS2	Rebecca Foulger Source NHS GMS was added to RARS2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RALA	Rebecca Foulger Source NHS GMS was added to RALA.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RAB18	Rebecca Foulger Source NHS GMS was added to RAB18.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RAB11B	Rebecca Foulger Source NHS GMS was added to RAB11B.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	QDPR	Rebecca Foulger Source NHS GMS was added to QDPR.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PTS	Rebecca Foulger Source NHS GMS was added to PTS.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PTPN23	Rebecca Foulger Source NHS GMS was added to PTPN23.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PTEN	Rebecca Foulger Source NHS GMS was added to PTEN.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PSAP	Rebecca Foulger Source NHS GMS was added to PSAP.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PRMT7	Rebecca Foulger Source NHS GMS was added to PRMT7.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PRICKLE1	Rebecca Foulger Source NHS GMS was added to PRICKLE1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PPT1	Rebecca Foulger Source NHS GMS was added to PPT1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PPP3CA	Rebecca Foulger Source NHS GMS was added to PPP3CA.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	POMT1	Rebecca Foulger Source NHS GMS was added to POMT1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	POMGNT1	Rebecca Foulger Source NHS GMS was added to POMGNT1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PMM2	Rebecca Foulger Source NHS GMS was added to PMM2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PLAA	Rebecca Foulger Source NHS GMS was added to PLAA.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PIK3R2	Rebecca Foulger Source NHS GMS was added to PIK3R2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PIK3CA	Rebecca Foulger Source NHS GMS was added to PIK3CA.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PIGW	Rebecca Foulger Source NHS GMS was added to PIGW.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PIGO	Rebecca Foulger Source NHS GMS was added to PIGO.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PIGG	Rebecca Foulger Source NHS GMS was added to PIGG.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PHGDH	Rebecca Foulger Source NHS GMS was added to PHGDH.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PHACTR1	Rebecca Foulger Source NHS GMS was added to PHACTR1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PEX7	Rebecca Foulger Source NHS GMS was added to PEX7.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PEX6	Rebecca Foulger Source NHS GMS was added to PEX6.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PEX3	Rebecca Foulger Source NHS GMS was added to PEX3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PEX2	Rebecca Foulger Source NHS GMS was added to PEX2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PEX19	Rebecca Foulger Source NHS GMS was added to PEX19.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PEX13	Rebecca Foulger Source NHS GMS was added to PEX13.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PEX12	Rebecca Foulger Source NHS GMS was added to PEX12.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PEX10	Rebecca Foulger Source NHS GMS was added to PEX10.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PEX1	Rebecca Foulger Source NHS GMS was added to PEX1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PET100	Rebecca Foulger Source NHS GMS was added to PET100.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PDHX	Rebecca Foulger Source NHS GMS was added to PDHX.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PDHA1	Rebecca Foulger Source NHS GMS was added to PDHA1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PCDH12	Rebecca Foulger Source NHS GMS was added to PCDH12.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PCCB	Rebecca Foulger Source NHS GMS was added to PCCB.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PCCA	Rebecca Foulger Source NHS GMS was added to PCCA.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PAH	Rebecca Foulger Source NHS GMS was added to PAH.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PAFAH1B1	Rebecca Foulger Source NHS GMS was added to PAFAH1B1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PACS2	Rebecca Foulger Source NHS GMS was added to PACS2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PACS1	Rebecca Foulger Source NHS GMS was added to PACS1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	OTUD6B	Rebecca Foulger Source NHS GMS was added to OTUD6B.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	OPHN1	Rebecca Foulger Source NHS GMS was added to OPHN1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	OCLN	Rebecca Foulger Source NHS GMS was added to OCLN.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NTRK2	Rebecca Foulger Source NHS GMS was added to NTRK2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NSDHL	Rebecca Foulger Source NHS GMS was added to NSDHL.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NSD1	Rebecca Foulger Source NHS GMS was added to NSD1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NRXN1	Rebecca Foulger Source NHS GMS was added to NRXN1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NPRL3	Rebecca Foulger Source NHS GMS was added to NPRL3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NHLRC1	Rebecca Foulger Source NHS GMS was added to NHLRC1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NGLY1	Rebecca Foulger Source NHS GMS was added to NGLY1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NDUFV1	Rebecca Foulger Source NHS GMS was added to NDUFV1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NDUFS8	Rebecca Foulger Source NHS GMS was added to NDUFS8.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NDUFS4	Rebecca Foulger Source NHS GMS was added to NDUFS4.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NDUFAF5	Rebecca Foulger Source NHS GMS was added to NDUFAF5.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NDUFAF2	Rebecca Foulger Source NHS GMS was added to NDUFAF2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NDUFA10	Rebecca Foulger Source NHS GMS was added to NDUFA10.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NDUFA1	Rebecca Foulger Source NHS GMS was added to NDUFA1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NDE1	Rebecca Foulger Source NHS GMS was added to NDE1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NARS2	Rebecca Foulger Source NHS GMS was added to NARS2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NAGA	Rebecca Foulger Source NHS GMS was added to NAGA.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MTR	Rebecca Foulger Source NHS GMS was added to MTR.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MTHFR	Rebecca Foulger Source NHS GMS was added to MTHFR.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MPDU1	Rebecca Foulger Source NHS GMS was added to MPDU1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MOCS2	Rebecca Foulger Source NHS GMS was added to MOCS2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MOCS1	Rebecca Foulger Source NHS GMS was added to MOCS1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MMADHC	Rebecca Foulger Source NHS GMS was added to MMADHC.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MMACHC	Rebecca Foulger Source NHS GMS was added to MMACHC.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MLC1	Rebecca Foulger Source NHS GMS was added to MLC1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MFSD8	Rebecca Foulger Source NHS GMS was added to MFSD8.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MED12	Rebecca Foulger Source NHS GMS was added to MED12.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MAP2K2	Rebecca Foulger Source NHS GMS was added to MAP2K2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MAP2K1	Rebecca Foulger Source NHS GMS was added to MAP2K1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MAGI2	Rebecca Foulger Source NHS GMS was added to MAGI2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MAF	Rebecca Foulger Source NHS GMS was added to MAF.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MACF1	Rebecca Foulger Source NHS GMS was added to MACF1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	LYST	Rebecca Foulger Source NHS GMS was added to LYST.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	LIAS	Rebecca Foulger Source NHS GMS was added to LIAS.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KRAS	Rebecca Foulger Source NHS GMS was added to KRAS.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KIF5C	Rebecca Foulger Source NHS GMS was added to KIF5C.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KIF2A	Rebecca Foulger Source NHS GMS was added to KIF2A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KIF1A	Rebecca Foulger Source NHS GMS was added to KIF1A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KCTD3	Rebecca Foulger Source NHS GMS was added to KCTD3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KCNQ5	Rebecca Foulger Source NHS GMS was added to KCNQ5.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KCNK4	Rebecca Foulger Source NHS GMS was added to KCNK4.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KCNJ11	Rebecca Foulger Source NHS GMS was added to KCNJ11.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KCNA1	Rebecca Foulger Source NHS GMS was added to KCNA1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KARS	Rebecca Foulger Source NHS GMS was added to KARS.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	IRF2BPL	Rebecca Foulger Source NHS GMS was added to IRF2BPL.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	IKBKG	Rebecca Foulger Source NHS GMS was added to IKBKG.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	IFIH1	Rebecca Foulger Source NHS GMS was added to IFIH1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	HSD17B4	Rebecca Foulger Source NHS GMS was added to HSD17B4.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	HRAS	Rebecca Foulger Source NHS GMS was added to HRAS.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	HLCS	Rebecca Foulger Source NHS GMS was added to HLCS.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	HEXA	Rebecca Foulger Source NHS GMS was added to HEXA.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	HEPACAM	Rebecca Foulger Source NHS GMS was added to HEPACAM.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	HCN2	Rebecca Foulger Source NHS GMS was added to HCN2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	HCFC1	Rebecca Foulger Source NHS GMS was added to HCFC1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	HAX1	Rebecca Foulger Source NHS GMS was added to HAX1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	HACE1	Rebecca Foulger Source NHS GMS was added to HACE1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GTPBP2	Rebecca Foulger Source NHS GMS was added to GTPBP2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GRIN2D	Rebecca Foulger Source NHS GMS was added to GRIN2D.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GRIA4	Rebecca Foulger Source NHS GMS was added to GRIA4.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GPHN	Rebecca Foulger Source NHS GMS was added to GPHN.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GOSR2	Rebecca Foulger Source NHS GMS was added to GOSR2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GNB5	Rebecca Foulger Source NHS GMS was added to GNB5.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GNB1	Rebecca Foulger Source NHS GMS was added to GNB1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GNAQ	Rebecca Foulger Source NHS GMS was added to GNAQ.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GM2A	Rebecca Foulger Source NHS GMS was added to GM2A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GLUL	Rebecca Foulger Source NHS GMS was added to GLUL.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GLUD1	Rebecca Foulger Source NHS GMS was added to GLUD1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GLDC	Rebecca Foulger Source NHS GMS was added to GLDC.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GLB1	Rebecca Foulger Source NHS GMS was added to GLB1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GFM1	Rebecca Foulger Source NHS GMS was added to GFM1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GFAP	Rebecca Foulger Source NHS GMS was added to GFAP.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GCH1	Rebecca Foulger Source NHS GMS was added to GCH1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GBA	Rebecca Foulger Source NHS GMS was added to GBA.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GAMT	Rebecca Foulger Source NHS GMS was added to GAMT.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GALC	Rebecca Foulger Source NHS GMS was added to GALC.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GABRB2	Rebecca Foulger Source NHS GMS was added to GABRB2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	FUT8	Rebecca Foulger Source NHS GMS was added to FUT8.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	FUCA1	Rebecca Foulger Source NHS GMS was added to FUCA1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	FRRS1L	Rebecca Foulger Source NHS GMS was added to FRRS1L.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	FOLR1	Rebecca Foulger Source NHS GMS was added to FOLR1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	FLNA	Rebecca Foulger Source NHS GMS was added to FLNA.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	FKTN	Rebecca Foulger Source NHS GMS was added to FKTN.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	FH	Rebecca Foulger Source NHS GMS was added to FH.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	FGFR3	Rebecca Foulger Source NHS GMS was added to FGFR3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	FGF12	Rebecca Foulger Source NHS GMS was added to FGF12.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	FBXO11	Rebecca Foulger Source NHS GMS was added to FBXO11.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	FBXL4	Rebecca Foulger Source NHS GMS was added to FBXL4.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	FARS2	Rebecca Foulger Source NHS GMS was added to FARS2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	FAR1	Rebecca Foulger Source NHS GMS was added to FAR1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	EXOSC3	Rebecca Foulger Source NHS GMS was added to EXOSC3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ETHE1	Rebecca Foulger Source NHS GMS was added to ETHE1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	EMX2	Rebecca Foulger Source NHS GMS was added to EMX2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	EIF3F	Rebecca Foulger Source NHS GMS was added to EIF3F.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	EIF2S3	Rebecca Foulger Source NHS GMS was added to EIF2S3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	EIF2B5	Rebecca Foulger Source NHS GMS was added to EIF2B5.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	EIF2B4	Rebecca Foulger Source NHS GMS was added to EIF2B4.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	EIF2B2	Rebecca Foulger Source NHS GMS was added to EIF2B2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	EFTUD2	Rebecca Foulger Source NHS GMS was added to EFTUD2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	EEF1A2	Rebecca Foulger Source NHS GMS was added to EEF1A2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	EARS2	Rebecca Foulger Source NHS GMS was added to EARS2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DYNC1H1	Rebecca Foulger Source NHS GMS was added to DYNC1H1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DPM1	Rebecca Foulger Source NHS GMS was added to DPM1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DPAGT1	Rebecca Foulger Source NHS GMS was added to DPAGT1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DNM1L	Rebecca Foulger Source NHS GMS was added to DNM1L.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DHX30	Rebecca Foulger Source NHS GMS was added to DHX30.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DHDDS	Rebecca Foulger Source NHS GMS was added to DHDDS.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DHCR7	Rebecca Foulger Source NHS GMS was added to DHCR7.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DENND5A	Rebecca Foulger Source NHS GMS was added to DENND5A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DEAF1	Rebecca Foulger Source NHS GMS was added to DEAF1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DDX3X	Rebecca Foulger Source NHS GMS was added to DDX3X.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DCX	Rebecca Foulger Source NHS GMS was added to DCX.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	D2HGDH	Rebecca Foulger Source NHS GMS was added to D2HGDH.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CTSD	Rebecca Foulger Source NHS GMS was added to CTSD.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CSTB	Rebecca Foulger Source NHS GMS was added to CSTB.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CREBBP	Rebecca Foulger Source NHS GMS was added to CREBBP.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	COQ9	Rebecca Foulger Source NHS GMS was added to COQ9.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	COQ4	Rebecca Foulger Source NHS GMS was added to COQ4.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	COQ2	Rebecca Foulger Source NHS GMS was added to COQ2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	COL4A2	Rebecca Foulger Source NHS GMS was added to COL4A2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	COL4A1	Rebecca Foulger Source NHS GMS was added to COL4A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	COL18A1	Rebecca Foulger Source NHS GMS was added to COL18A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	COG7	Rebecca Foulger Source NHS GMS was added to COG7.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CNNM2	Rebecca Foulger Source NHS GMS was added to CNNM2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CLN3	Rebecca Foulger Source NHS GMS was added to CLN3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CLCN4	Rebecca Foulger Source NHS GMS was added to CLCN4.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CC2D2A	Rebecca Foulger Source NHS GMS was added to CC2D2A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CASK	Rebecca Foulger Source NHS GMS was added to CASK.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CAD	Rebecca Foulger Source NHS GMS was added to CAD.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CACNA1G	Rebecca Foulger Source NHS GMS was added to CACNA1G.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CACNA1E	Rebecca Foulger Source NHS GMS was added to CACNA1E.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CACNA1A	Rebecca Foulger Source NHS GMS was added to CACNA1A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	C12orf57	Rebecca Foulger Source NHS GMS was added to C12orf57.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	BTD	Rebecca Foulger Source NHS GMS was added to BTD.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	BRAF	Rebecca Foulger Source NHS GMS was added to BRAF.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	BOLA3	Rebecca Foulger Source NHS GMS was added to BOLA3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	BCS1L	Rebecca Foulger Source NHS GMS was added to BCS1L.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	BCKDHB	Rebecca Foulger Source NHS GMS was added to BCKDHB.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	BCKDHA	Rebecca Foulger Source NHS GMS was added to BCKDHA.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ATP7A	Rebecca Foulger Source NHS GMS was added to ATP7A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ATP6V1A	Rebecca Foulger Source NHS GMS was added to ATP6V1A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ATP1A1	Rebecca Foulger Source NHS GMS was added to ATP1A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ASPA	Rebecca Foulger Source NHS GMS was added to ASPA.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ARV1	Rebecca Foulger Source NHS GMS was added to ARV1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ARID1B	Rebecca Foulger Source NHS GMS was added to ARID1B.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ARG1	Rebecca Foulger Source NHS GMS was added to ARG1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ARFGEF2	Rebecca Foulger Source NHS GMS was added to ARFGEF2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	AP3B2	Rebecca Foulger Source NHS GMS was added to AP3B2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	AMT	Rebecca Foulger Source NHS GMS was added to AMT.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	AMPD2	Rebecca Foulger Source NHS GMS was added to AMPD2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ALPL	Rebecca Foulger Source NHS GMS was added to ALPL.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ALG9	Rebecca Foulger Source NHS GMS was added to ALG9.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ALG8	Rebecca Foulger Source NHS GMS was added to ALG8.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ALG6	Rebecca Foulger Source NHS GMS was added to ALG6.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ALG3	Rebecca Foulger Source NHS GMS was added to ALG3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ALG1	Rebecca Foulger Source NHS GMS was added to ALG1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ALDH5A1	Rebecca Foulger Source NHS GMS was added to ALDH5A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	AKT3	Rebecca Foulger Source NHS GMS was added to AKT3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	AKT1	Rebecca Foulger Source NHS GMS was added to AKT1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	AIMP1	Rebecca Foulger Source NHS GMS was added to AIMP1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ADPRHL2	Rebecca Foulger Source NHS GMS was added to ADPRHL2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ADGRG1	Rebecca Foulger Source NHS GMS was added to ADGRG1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ADAR	Rebecca Foulger Source NHS GMS was added to ADAR.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ACOX1	Rebecca Foulger Source NHS GMS was added to ACOX1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ABAT	Rebecca Foulger Source NHS GMS was added to ABAT.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ZEB2	Rebecca Foulger Source NHS GMS was added to ZEB2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	WWOX	Rebecca Foulger Source NHS GMS was added to WWOX.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	WDR45B	Rebecca Foulger Source NHS GMS was added to WDR45B.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	WDR45	Rebecca Foulger Source NHS GMS was added to WDR45.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	UBE3A	Rebecca Foulger Source NHS GMS was added to UBE3A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	UBE2A	Rebecca Foulger Source NHS GMS was added to UBE2A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TRPM6	Rebecca Foulger Source NHS GMS was added to TRPM6.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TRAK1	Rebecca Foulger Source NHS GMS was added to TRAK1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TPP1	Rebecca Foulger Source NHS GMS was added to TPP1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TCF4	Rebecca Foulger Source NHS GMS was added to TCF4.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	TBC1D24	Rebecca Foulger Source NHS GMS was added to TBC1D24.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SZT2	Rebecca Foulger Source NHS GMS was added to SZT2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SYNJ1	Rebecca Foulger Source NHS GMS was added to SYNJ1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SYNGAP1	Rebecca Foulger Source NHS GMS was added to SYNGAP1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SUOX	Rebecca Foulger Source NHS GMS was added to SUOX.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	STXBP1	Rebecca Foulger Source NHS GMS was added to STXBP1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	STX1B	Rebecca Foulger Source NHS GMS was added to STX1B.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	STRADA	Rebecca Foulger Source NHS GMS was added to STRADA.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SPTAN1	Rebecca Foulger Source NHS GMS was added to SPTAN1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SLC9A6	Rebecca Foulger Source NHS GMS was added to SLC9A6.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SLC6A19	Rebecca Foulger Source NHS GMS was added to SLC6A19.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SLC6A1	Rebecca Foulger Source NHS GMS was added to SLC6A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SLC35A2	Rebecca Foulger Source NHS GMS was added to SLC35A2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SLC2A1	Rebecca Foulger Source NHS GMS was added to SLC2A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SLC25A22	Rebecca Foulger Source NHS GMS was added to SLC25A22.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SLC25A1	Rebecca Foulger Source NHS GMS was added to SLC25A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SLC1A2	Rebecca Foulger Source NHS GMS was added to SLC1A2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SLC16A2	Rebecca Foulger Source NHS GMS was added to SLC16A2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SLC13A5	Rebecca Foulger Source NHS GMS was added to SLC13A5.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SLC12A5	Rebecca Foulger Source NHS GMS was added to SLC12A5.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SIK1	Rebecca Foulger Source NHS GMS was added to SIK1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SETD5	Rebecca Foulger Source NHS GMS was added to SETD5.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SCN9A	Rebecca Foulger Source NHS GMS was added to SCN9A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SCN8A	Rebecca Foulger Source NHS GMS was added to SCN8A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SCN2A	Rebecca Foulger Source NHS GMS was added to SCN2A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SCN1B	Rebecca Foulger Source NHS GMS was added to SCN1B.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SCN1A	Rebecca Foulger Source NHS GMS was added to SCN1A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	SCARB2	Rebecca Foulger Source NHS GMS was added to SCARB2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	RANBP2	Rebecca Foulger Source NHS GMS was added to RANBP2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	QARS	Rebecca Foulger Source NHS GMS was added to QARS.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PURA	Rebecca Foulger Source NHS GMS was added to PURA.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PRRT2	Rebecca Foulger Source NHS GMS was added to PRRT2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PRODH	Rebecca Foulger Source NHS GMS was added to PRODH.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	POLG	Rebecca Foulger Source NHS GMS was added to POLG.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PNPO	Rebecca Foulger Source NHS GMS was added to PNPO.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PNKP	Rebecca Foulger Source NHS GMS was added to PNKP.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PLPBP	Rebecca Foulger Source NHS GMS was added to PLPBP.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PLCB1	Rebecca Foulger Source NHS GMS was added to PLCB1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PIGT	Rebecca Foulger Source NHS GMS was added to PIGT.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PIGN	Rebecca Foulger Source NHS GMS was added to PIGN.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PIGA	Rebecca Foulger Source NHS GMS was added to PIGA.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	PCDH19	Rebecca Foulger Source NHS GMS was added to PCDH19.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NEXMIF	Rebecca Foulger Source NHS GMS was added to NEXMIF.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	NACC1	Rebecca Foulger Source NHS GMS was added to NACC1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MTOR	Rebecca Foulger Source NHS GMS was added to MTOR.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MOGS	Rebecca Foulger Source NHS GMS was added to MOGS.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MFF	Rebecca Foulger Source NHS GMS was added to MFF.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MEF2C	Rebecca Foulger Source NHS GMS was added to MEF2C.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MECP2	Rebecca Foulger Source NHS GMS was added to MECP2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MDH2	Rebecca Foulger Source NHS GMS was added to MDH2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MBOAT7	Rebecca Foulger Source NHS GMS was added to MBOAT7.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	MBD5	Rebecca Foulger Source NHS GMS was added to MBD5.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	LGI1	Rebecca Foulger Source NHS GMS was added to LGI1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KIF1BP	Rebecca Foulger Source NHS GMS was added to KIF1BP.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KCTD7	Rebecca Foulger Source NHS GMS was added to KCTD7.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KCNT1	Rebecca Foulger Source NHS GMS was added to KCNT1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KCNQ3	Rebecca Foulger Source NHS GMS was added to KCNQ3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KCNQ2	Rebecca Foulger Source NHS GMS was added to KCNQ2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KCNJ10	Rebecca Foulger Source NHS GMS was added to KCNJ10.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KCNC1	Rebecca Foulger Source NHS GMS was added to KCNC1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KCNB1	Rebecca Foulger Source NHS GMS was added to KCNB1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	KCNA2	Rebecca Foulger Source NHS GMS was added to KCNA2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ITPA	Rebecca Foulger Source NHS GMS was added to ITPA.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	IQSEC2	Rebecca Foulger Source NHS GMS was added to IQSEC2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	IER3IP1	Rebecca Foulger Source NHS GMS was added to IER3IP1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	IDH2	Rebecca Foulger Source NHS GMS was added to IDH2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	HTRA2	Rebecca Foulger Source NHS GMS was added to HTRA2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	HNRNPU	Rebecca Foulger Source NHS GMS was added to HNRNPU.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	HNRNPH2	Rebecca Foulger Source NHS GMS was added to HNRNPH2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	HMGCL	Rebecca Foulger Source NHS GMS was added to HMGCL.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	HECW2	Rebecca Foulger Source NHS GMS was added to HECW2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	HCN1	Rebecca Foulger Source NHS GMS was added to HCN1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GSS	Rebecca Foulger Source NHS GMS was added to GSS.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GRIN2B	Rebecca Foulger Source NHS GMS was added to GRIN2B.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GRIN2A	Rebecca Foulger Source NHS GMS was added to GRIN2A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GRIN1	Rebecca Foulger Source NHS GMS was added to GRIN1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GPAA1	Rebecca Foulger Source NHS GMS was added to GPAA1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GNAO1	Rebecca Foulger Source NHS GMS was added to GNAO1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GLYCTK	Rebecca Foulger Source NHS GMS was added to GLYCTK.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GABRG2	Rebecca Foulger Source NHS GMS was added to GABRG2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GABRB3	Rebecca Foulger Source NHS GMS was added to GABRB3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GABRA1	Rebecca Foulger Source NHS GMS was added to GABRA1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	GABBR2	Rebecca Foulger Source NHS GMS was added to GABBR2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	FOXG1	Rebecca Foulger Source NHS GMS was added to FOXG1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	EPM2A	Rebecca Foulger Source NHS GMS was added to EPM2A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	EPG5	Rebecca Foulger Source NHS GMS was added to EPG5.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	EML1	Rebecca Foulger Source NHS GMS was added to EML1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	EHMT1	Rebecca Foulger Source NHS GMS was added to EHMT1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DYRK1A	Rebecca Foulger Source NHS GMS was added to DYRK1A.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DPYD	Rebecca Foulger Source NHS GMS was added to DPYD.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DOCK7	Rebecca Foulger Source NHS GMS was added to DOCK7.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DNM1	Rebecca Foulger Source NHS GMS was added to DNM1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DIAPH1	Rebecca Foulger Source NHS GMS was added to DIAPH1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	DEPDC5	Rebecca Foulger Source NHS GMS was added to DEPDC5.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CYFIP2	Rebecca Foulger Source NHS GMS was added to CYFIP2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CPA6	Rebecca Foulger Source NHS GMS was added to CPA6.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CNTNAP2	Rebecca Foulger Source NHS GMS was added to CNTNAP2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CNKSR2	Rebecca Foulger Source NHS GMS was added to CNKSR2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CLTC	Rebecca Foulger Source NHS GMS was added to CLTC.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CLN8	Rebecca Foulger Source NHS GMS was added to CLN8.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CIC	Rebecca Foulger Source NHS GMS was added to CIC.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CHRNB2	Rebecca Foulger Source NHS GMS was added to CHRNB2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CHRNA4	Rebecca Foulger Source NHS GMS was added to CHRNA4.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CHRNA2	Rebecca Foulger Source NHS GMS was added to CHRNA2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CHD2	Rebecca Foulger Source NHS GMS was added to CHD2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CDKL5	Rebecca Foulger Source NHS GMS was added to CDKL5.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	CACNA1D	Rebecca Foulger Source NHS GMS was added to CACNA1D.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	BSCL2	Rebecca Foulger Source NHS GMS was added to BSCL2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	BRAT1	Rebecca Foulger Source NHS GMS was added to BRAT1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ATRX	Rebecca Foulger Source NHS GMS was added to ATRX.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ATP6V0A2	Rebecca Foulger Source NHS GMS was added to ATP6V0A2.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ATP1A3	Rebecca Foulger Source NHS GMS was added to ATP1A3.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ARX	Rebecca Foulger Source NHS GMS was added to ARX.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ARHGEF9	Rebecca Foulger Source NHS GMS was added to ARHGEF9.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ALG13	Rebecca Foulger Source NHS GMS was added to ALG13.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ALG11	Rebecca Foulger Source NHS GMS was added to ALG11.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ALDH7A1	Rebecca Foulger Source NHS GMS was added to ALDH7A1.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	ADSL	Rebecca Foulger Source NHS GMS was added to ADSL.
06 Aug 2019	Early onset or syndromic epilepsy v1.190	AARS	Rebecca Foulger Source NHS GMS was added to AARS.
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ZIC2	Rebecca Foulger reviewed gene: ZIC2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TGIF1	Rebecca Foulger reviewed gene: TGIF1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	STIL	Rebecca Foulger reviewed gene: STIL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SLC25A19	Rebecca Foulger reviewed gene: SLC25A19: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PTCH1	Rebecca Foulger reviewed gene: PTCH1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PRDM8	Rebecca Foulger reviewed gene: PRDM8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	LMNB2	Rebecca Foulger reviewed gene: LMNB2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GUF1	Rebecca Foulger reviewed gene: GUF1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GABRB1	Rebecca Foulger reviewed gene: GABRB1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CUL4B	Rebecca Foulger edited their review of gene: CUL4B: Added comment: This gene was part of an initial gene list collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CTSF	Rebecca Foulger reviewed gene: CTSF: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CERS1	Rebecca Foulger reviewed gene: CERS1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ADRA2B	Rebecca Foulger reviewed gene: ADRA2B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TUBA3E	Rebecca Foulger reviewed gene: TUBA3E: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SLC6A5	Rebecca Foulger reviewed gene: SLC6A5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SHH	Rebecca Foulger reviewed gene: SHH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SEC24D	Rebecca Foulger reviewed gene: SEC24D: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SCN2B	Rebecca Foulger reviewed gene: SCN2B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RYR3	Rebecca Foulger reviewed gene: RYR3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RUBCN	Rebecca Foulger reviewed gene: RUBCN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PSMB8	Rebecca Foulger reviewed gene: PSMB8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PRICKLE2	Rebecca Foulger reviewed gene: PRICKLE2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PCDHB4	Rebecca Foulger reviewed gene: PCDHB4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NRAS	Rebecca Foulger reviewed gene: NRAS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NID1	Rebecca Foulger reviewed gene: NID1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NDUFA11	Rebecca Foulger reviewed gene: NDUFA11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MT-TL1	Rebecca Foulger reviewed gene: MT-TL1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MATN4	Rebecca Foulger reviewed gene: MATN4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MAPK10	Rebecca Foulger reviewed gene: MAPK10: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KAT5	Rebecca Foulger reviewed gene: KAT5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	INO80	Rebecca Foulger reviewed gene: INO80: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	H3F3B	Rebecca Foulger reviewed gene: H3F3B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	H3F3A	Rebecca Foulger reviewed gene: H3F3A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GLRB	Rebecca Foulger reviewed gene: GLRB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GCSH	Rebecca Foulger reviewed gene: GCSH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GATM	Rebecca Foulger reviewed gene: GATM: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GATAD2B	Rebecca Foulger reviewed gene: GATAD2B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GAL	Rebecca Foulger reviewed gene: GAL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GABRD	Rebecca Foulger reviewed gene: GABRD: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	FTL	Rebecca Foulger reviewed gene: FTL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	FIG4	Rebecca Foulger reviewed gene: FIG4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DMBX1	Rebecca Foulger reviewed gene: DMBX1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CYP27A1	Rebecca Foulger edited their review of gene: CYP27A1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CSNK1G1	Rebecca Foulger reviewed gene: CSNK1G1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CRH	Rebecca Foulger reviewed gene: CRH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CNTN2	Rebecca Foulger reviewed gene: CNTN2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CLN6	Rebecca Foulger reviewed gene: CLN6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CLN5	Rebecca Foulger reviewed gene: CLN5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CLCN2	Rebecca Foulger reviewed gene: CLCN2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CBL	Rebecca Foulger reviewed gene: CBL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CASR	Rebecca Foulger reviewed gene: CASR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CAMK2G	Rebecca Foulger reviewed gene: CAMK2G: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CACNB4	Rebecca Foulger reviewed gene: CACNB4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ASAH1	Rebecca Foulger edited their review of gene: ASAH1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ALG2	Rebecca Foulger reviewed gene: ALG2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ALG12	Rebecca Foulger reviewed gene: ALG12: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ADGRV1	Rebecca Foulger reviewed gene: ADGRV1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	AARS2	Rebecca Foulger reviewed gene: AARS2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	VLDLR	Rebecca Foulger reviewed gene: VLDLR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	UFC1	Rebecca Foulger reviewed gene: UFC1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TXNRD1	Rebecca Foulger reviewed gene: TXNRD1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TUBB	Rebecca Foulger edited their review of gene: TUBB: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TUBA8	Rebecca Foulger edited their review of gene: TUBA8: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TSFM	Rebecca Foulger edited their review of gene: TSFM: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TSEN34	Rebecca Foulger edited their review of gene: TSEN34: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TSEN15	Rebecca Foulger edited their review of gene: TSEN15: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TRIP13	Rebecca Foulger edited their review of gene: TRIP13: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TRAPPC6B	Rebecca Foulger edited their review of gene: TRAPPC6B: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TRAPPC12	Rebecca Foulger edited their review of gene: TRAPPC12: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TRAF7	Rebecca Foulger edited their review of gene: TRAF7: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TNK2	Rebecca Foulger edited their review of gene: TNK2: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TIMM50	Rebecca Foulger edited their review of gene: TIMM50: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TFE3	Rebecca Foulger reviewed gene: TFE3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TELO2	Rebecca Foulger reviewed gene: TELO2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TBC1D20	Rebecca Foulger edited their review of gene: TBC1D20: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SUCLG1	Rebecca Foulger edited their review of gene: SUCLG1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ST3GAL3	Rebecca Foulger reviewed gene: ST3GAL3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SRPX2	Rebecca Foulger reviewed gene: SRPX2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SPR	Rebecca Foulger reviewed gene: SPR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SNIP1	Rebecca Foulger reviewed gene: SNIP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SMC1A	Rebecca Foulger edited their review of gene: SMC1A: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SLC45A1	Rebecca Foulger reviewed gene: SLC45A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SLC35A1	Rebecca Foulger edited their review of gene: SLC35A1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SIX3	Rebecca Foulger reviewed gene: SIX3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SETD1B	Rebecca Foulger reviewed gene: SETD1B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SDHA	Rebecca Foulger reviewed gene: SDHA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RYR2	Rebecca Foulger reviewed gene: RYR2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RUSC2	Rebecca Foulger reviewed gene: RUSC2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RRM2B	Rebecca Foulger edited their review of gene: RRM2B: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RPIA	Rebecca Foulger reviewed gene: RPIA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RNU4ATAC	Rebecca Foulger reviewed gene: RNU4ATAC: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RAB3GAP2	Rebecca Foulger reviewed gene: RAB3GAP2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RAB3GAP1	Rebecca Foulger reviewed gene: RAB3GAP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PTF1A	Rebecca Foulger edited their review of gene: PTF1A: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PSPH	Rebecca Foulger reviewed gene: PSPH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PSAT1	Rebecca Foulger reviewed gene: PSAT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	POMT2	Rebecca Foulger reviewed gene: POMT2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PIGQ	Rebecca Foulger reviewed gene: PIGQ: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PIGH	Rebecca Foulger edited their review of gene: PIGH: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PIGC	Rebecca Foulger edited their review of gene: PIGC: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PEX5	Rebecca Foulger edited their review of gene: PEX5: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PDSS2	Rebecca Foulger reviewed gene: PDSS2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PCLO	Rebecca Foulger reviewed gene: PCLO: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	OTX2	Rebecca Foulger reviewed gene: OTX2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NUBPL	Rebecca Foulger reviewed gene: NUBPL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NPRL2	Rebecca Foulger edited their review of gene: NPRL2: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NEDD4L	Rebecca Foulger reviewed gene: NEDD4L: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NECAP1	Rebecca Foulger edited their review of gene: NECAP1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NDUFS7	Rebecca Foulger reviewed gene: NDUFS7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NDUFS6	Rebecca Foulger reviewed gene: NDUFS6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NDUFS2	Rebecca Foulger reviewed gene: NDUFS2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NDUFS1	Rebecca Foulger reviewed gene: NDUFS1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NDUFAF4	Rebecca Foulger reviewed gene: NDUFAF4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NDUFAF3	Rebecca Foulger reviewed gene: NDUFAF3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NDUFA2	Rebecca Foulger reviewed gene: NDUFA2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NDP	Rebecca Foulger reviewed gene: NDP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MED17	Rebecca Foulger reviewed gene: MED17: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MAST1	Rebecca Foulger edited their review of gene: MAST1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Red. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MANBA	Rebecca Foulger reviewed gene: MANBA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	LNPK	Rebecca Foulger reviewed gene: LNPK: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	LIPT2	Rebecca Foulger reviewed gene: LIPT2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	LARGE1	Rebecca Foulger reviewed gene: LARGE1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KPTN	Rebecca Foulger edited their review of gene: KPTN: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KIAA1109	Rebecca Foulger edited their review of gene: KIAA1109: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KCNMA1	Rebecca Foulger edited their review of gene: KCNMA1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ISPD	Rebecca Foulger reviewed gene: ISPD: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	HSPD1	Rebecca Foulger reviewed gene: HSPD1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	HPRT1	Rebecca Foulger reviewed gene: HPRT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	HOXA1	Rebecca Foulger edited their review of gene: HOXA1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Red. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	HEXB	Rebecca Foulger edited their review of gene: HEXB: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	HCCS	Rebecca Foulger reviewed gene: HCCS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GTPBP3	Rebecca Foulger reviewed gene: GTPBP3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GLRA1	Rebecca Foulger reviewed gene: GLRA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GLI3	Rebecca Foulger reviewed gene: GLI3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	FOXRED1	Rebecca Foulger reviewed gene: FOXRED1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	FKRP	Rebecca Foulger reviewed gene: FKRP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	FASTKD2	Rebecca Foulger reviewed gene: FASTKD2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	EIF2B3	Rebecca Foulger edited their review of gene: EIF2B3: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	EIF2B1	Rebecca Foulger edited their review of gene: EIF2B1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	EFHC1	Rebecca Foulger edited their review of gene: EFHC1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DPM2	Rebecca Foulger edited their review of gene: DPM2: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DOLK	Rebecca Foulger edited their review of gene: DOLK: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DNAJC6	Rebecca Foulger reviewed gene: DNAJC6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DHCR24	Rebecca Foulger edited their review of gene: DHCR24: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DBT	Rebecca Foulger edited their review of gene: DBT: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CUX2	Rebecca Foulger edited their review of gene: CUX2: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CSNK2B	Rebecca Foulger edited their review of gene: CSNK2B: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	COX15	Rebecca Foulger reviewed gene: COX15: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	COX10	Rebecca Foulger reviewed gene: COX10: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	COQ6	Rebecca Foulger reviewed gene: COQ6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	COG8	Rebecca Foulger reviewed gene: COG8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	COG6	Rebecca Foulger reviewed gene: COG6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	COG4	Rebecca Foulger reviewed gene: COG4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CNPY3	Rebecca Foulger edited their review of gene: CNPY3: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CCND2	Rebecca Foulger reviewed gene: CCND2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CCDC88C	Rebecca Foulger reviewed gene: CCDC88C: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CCDC88A	Rebecca Foulger reviewed gene: CCDC88A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CACNA2D2	Rebecca Foulger reviewed gene: CACNA2D2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CACNA1H	Rebecca Foulger reviewed gene: CACNA1H: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ATP6AP2	Rebecca Foulger reviewed gene: ATP6AP2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ATP5A1	Rebecca Foulger reviewed gene: ATP5A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ATP1A2	Rebecca Foulger edited their review of gene: ATP1A2: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ADAT3	Rebecca Foulger reviewed gene: ADAT3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ZBTB18	Rebecca Foulger reviewed gene: ZBTB18: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	YWHAG	Rebecca Foulger reviewed gene: YWHAG: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	WDR73	Rebecca Foulger reviewed gene: WDR73: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	WDR62	Rebecca Foulger reviewed gene: WDR62: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	WASF1	Rebecca Foulger reviewed gene: WASF1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	VARS	Rebecca Foulger reviewed gene: VARS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	UNC80	Rebecca Foulger reviewed gene: UNC80: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	UFM1	Rebecca Foulger reviewed gene: UFM1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	UBA5	Rebecca Foulger reviewed gene: UBA5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TUBG1	Rebecca Foulger reviewed gene: TUBG1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TUBB4A	Rebecca Foulger reviewed gene: TUBB4A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TUBB3	Rebecca Foulger edited their review of gene: TUBB3: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TUBB2B	Rebecca Foulger edited their review of gene: TUBB2B: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TUBB2A	Rebecca Foulger edited their review of gene: TUBB2A: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TUBA1A	Rebecca Foulger edited their review of gene: TUBA1A: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TSEN54	Rebecca Foulger edited their review of gene: TSEN54: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TSEN2	Rebecca Foulger edited their review of gene: TSEN2: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TSC2	Rebecca Foulger reviewed gene: TSC2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TSC1	Rebecca Foulger reviewed gene: TSC1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TRIM8	Rebecca Foulger edited their review of gene: TRIM8: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TREX1	Rebecca Foulger edited their review of gene: TREX1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TMEM70	Rebecca Foulger edited their review of gene: TMEM70: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TBL1XR1	Rebecca Foulger edited their review of gene: TBL1XR1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TBCK	Rebecca Foulger edited their review of gene: TBCK: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TBCD	Rebecca Foulger edited their review of gene: TBCD: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TANGO2	Rebecca Foulger reviewed gene: TANGO2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SYN1	Rebecca Foulger reviewed gene: SYN1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SURF1	Rebecca Foulger edited their review of gene: SURF1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SUCLA2	Rebecca Foulger edited their review of gene: SUCLA2: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	STAMBP	Rebecca Foulger reviewed gene: STAMBP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	STAG1	Rebecca Foulger reviewed gene: STAG1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ST3GAL5	Rebecca Foulger reviewed gene: ST3GAL5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SNORD118	Rebecca Foulger reviewed gene: SNORD118: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SMS	Rebecca Foulger reviewed gene: SMS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SMARCA2	Rebecca Foulger reviewed gene: SMARCA2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SLC6A8	Rebecca Foulger reviewed gene: SLC6A8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SLC25A12	Rebecca Foulger edited their review of gene: SLC25A12: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SLC1A4	Rebecca Foulger reviewed gene: SLC1A4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SETBP1	Rebecca Foulger reviewed gene: SETBP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SEPSECS	Rebecca Foulger reviewed gene: SEPSECS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SCO2	Rebecca Foulger reviewed gene: SCO2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SCO1	Rebecca Foulger reviewed gene: SCO1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SCN3A	Rebecca Foulger reviewed gene: SCN3A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SAMHD1	Rebecca Foulger edited their review of gene: SAMHD1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RTTN	Rebecca Foulger reviewed gene: RTTN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RTN4IP1	Rebecca Foulger reviewed gene: RTN4IP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RORB	Rebecca Foulger reviewed gene: RORB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RORA	Rebecca Foulger reviewed gene: RORA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ROGDI	Rebecca Foulger reviewed gene: ROGDI: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RNASET2	Rebecca Foulger reviewed gene: RNASET2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RNASEH2C	Rebecca Foulger edited their review of gene: RNASEH2C: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RNASEH2B	Rebecca Foulger edited their review of gene: RNASEH2B: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RNASEH2A	Rebecca Foulger edited their review of gene: RNASEH2A: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RMND1	Rebecca Foulger reviewed gene: RMND1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RHOBTB2	Rebecca Foulger reviewed gene: RHOBTB2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RFT1	Rebecca Foulger reviewed gene: RFT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RELN	Rebecca Foulger edited their review of gene: RELN: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RARS2	Rebecca Foulger reviewed gene: RARS2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RALA	Rebecca Foulger reviewed gene: RALA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RAB18	Rebecca Foulger reviewed gene: RAB18: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RAB11B	Rebecca Foulger reviewed gene: RAB11B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	QDPR	Rebecca Foulger reviewed gene: QDPR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PTS	Rebecca Foulger reviewed gene: PTS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PTPN23	Rebecca Foulger reviewed gene: PTPN23: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PTEN	Rebecca Foulger reviewed gene: PTEN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PSAP	Rebecca Foulger reviewed gene: PSAP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PRMT7	Rebecca Foulger reviewed gene: PRMT7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PRICKLE1	Rebecca Foulger edited their review of gene: PRICKLE1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PPT1	Rebecca Foulger reviewed gene: PPT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PPP3CA	Rebecca Foulger reviewed gene: PPP3CA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	POMT1	Rebecca Foulger reviewed gene: POMT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	POMGNT1	Rebecca Foulger reviewed gene: POMGNT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PMM2	Rebecca Foulger reviewed gene: PMM2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PLAA	Rebecca Foulger reviewed gene: PLAA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PIK3R2	Rebecca Foulger reviewed gene: PIK3R2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PIK3CA	Rebecca Foulger reviewed gene: PIK3CA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PIGW	Rebecca Foulger reviewed gene: PIGW: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PIGO	Rebecca Foulger reviewed gene: PIGO: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PIGG	Rebecca Foulger reviewed gene: PIGG: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PHGDH	Rebecca Foulger reviewed gene: PHGDH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PHACTR1	Rebecca Foulger reviewed gene: PHACTR1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PEX7	Rebecca Foulger reviewed gene: PEX7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PEX6	Rebecca Foulger reviewed gene: PEX6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PEX3	Rebecca Foulger reviewed gene: PEX3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PEX2	Rebecca Foulger reviewed gene: PEX2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PEX19	Rebecca Foulger reviewed gene: PEX19: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PEX13	Rebecca Foulger reviewed gene: PEX13: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PEX12	Rebecca Foulger reviewed gene: PEX12: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PEX10	Rebecca Foulger reviewed gene: PEX10: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PEX1	Rebecca Foulger reviewed gene: PEX1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PET100	Rebecca Foulger edited their review of gene: PET100: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PDHX	Rebecca Foulger reviewed gene: PDHX: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PDHA1	Rebecca Foulger reviewed gene: PDHA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PCDH12	Rebecca Foulger reviewed gene: PCDH12: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PCCB	Rebecca Foulger reviewed gene: PCCB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PCCA	Rebecca Foulger reviewed gene: PCCA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PAH	Rebecca Foulger reviewed gene: PAH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PAFAH1B1	Rebecca Foulger reviewed gene: PAFAH1B1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PACS2	Rebecca Foulger reviewed gene: PACS2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PACS1	Rebecca Foulger reviewed gene: PACS1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	OTUD6B	Rebecca Foulger reviewed gene: OTUD6B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	OPHN1	Rebecca Foulger reviewed gene: OPHN1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	OCLN	Rebecca Foulger reviewed gene: OCLN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NTRK2	Rebecca Foulger edited their review of gene: NTRK2: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NSDHL	Rebecca Foulger reviewed gene: NSDHL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NSD1	Rebecca Foulger reviewed gene: NSD1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NRXN1	Rebecca Foulger reviewed gene: NRXN1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NPRL3	Rebecca Foulger reviewed gene: NPRL3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NHLRC1	Rebecca Foulger reviewed gene: NHLRC1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NGLY1	Rebecca Foulger reviewed gene: NGLY1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NDUFV1	Rebecca Foulger reviewed gene: NDUFV1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NDUFS8	Rebecca Foulger reviewed gene: NDUFS8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NDUFS4	Rebecca Foulger reviewed gene: NDUFS4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NDUFAF5	Rebecca Foulger reviewed gene: NDUFAF5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NDUFAF2	Rebecca Foulger reviewed gene: NDUFAF2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NDUFA10	Rebecca Foulger reviewed gene: NDUFA10: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NDUFA1	Rebecca Foulger reviewed gene: NDUFA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NDE1	Rebecca Foulger reviewed gene: NDE1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NARS2	Rebecca Foulger reviewed gene: NARS2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NAGA	Rebecca Foulger reviewed gene: NAGA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MTR	Rebecca Foulger reviewed gene: MTR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MTHFR	Rebecca Foulger reviewed gene: MTHFR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MPDU1	Rebecca Foulger edited their review of gene: MPDU1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MOCS2	Rebecca Foulger reviewed gene: MOCS2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MOCS1	Rebecca Foulger reviewed gene: MOCS1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MMADHC	Rebecca Foulger edited their review of gene: MMADHC: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MMACHC	Rebecca Foulger edited their review of gene: MMACHC: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MLC1	Rebecca Foulger edited their review of gene: MLC1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MFSD8	Rebecca Foulger reviewed gene: MFSD8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MED12	Rebecca Foulger reviewed gene: MED12: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MAP2K2	Rebecca Foulger reviewed gene: MAP2K2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MAP2K1	Rebecca Foulger reviewed gene: MAP2K1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MAGI2	Rebecca Foulger reviewed gene: MAGI2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MAF	Rebecca Foulger reviewed gene: MAF: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MACF1	Rebecca Foulger reviewed gene: MACF1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	LYST	Rebecca Foulger reviewed gene: LYST: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	LIAS	Rebecca Foulger reviewed gene: LIAS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KRAS	Rebecca Foulger reviewed gene: KRAS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KIF5C	Rebecca Foulger reviewed gene: KIF5C: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KIF2A	Rebecca Foulger edited their review of gene: KIF2A: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KIF1A	Rebecca Foulger reviewed gene: KIF1A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KCTD3	Rebecca Foulger reviewed gene: KCTD3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KCNQ5	Rebecca Foulger reviewed gene: KCNQ5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KCNK4	Rebecca Foulger reviewed gene: KCNK4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KCNJ11	Rebecca Foulger reviewed gene: KCNJ11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KCNA1	Rebecca Foulger reviewed gene: KCNA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KARS	Rebecca Foulger reviewed gene: KARS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	IRF2BPL	Rebecca Foulger reviewed gene: IRF2BPL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	IKBKG	Rebecca Foulger reviewed gene: IKBKG: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	IFIH1	Rebecca Foulger edited their review of gene: IFIH1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	HSD17B4	Rebecca Foulger reviewed gene: HSD17B4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	HRAS	Rebecca Foulger reviewed gene: HRAS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	HLCS	Rebecca Foulger reviewed gene: HLCS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	HEXA	Rebecca Foulger reviewed gene: HEXA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	HEPACAM	Rebecca Foulger reviewed gene: HEPACAM: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	HCN2	Rebecca Foulger edited their review of gene: HCN2: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	HCFC1	Rebecca Foulger reviewed gene: HCFC1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	HAX1	Rebecca Foulger reviewed gene: HAX1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	HACE1	Rebecca Foulger reviewed gene: HACE1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GTPBP2	Rebecca Foulger reviewed gene: GTPBP2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GRIN2D	Rebecca Foulger reviewed gene: GRIN2D: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GRIA4	Rebecca Foulger reviewed gene: GRIA4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GPHN	Rebecca Foulger reviewed gene: GPHN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GOSR2	Rebecca Foulger reviewed gene: GOSR2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GNB5	Rebecca Foulger reviewed gene: GNB5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GNB1	Rebecca Foulger reviewed gene: GNB1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GNAQ	Rebecca Foulger reviewed gene: GNAQ: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GM2A	Rebecca Foulger reviewed gene: GM2A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GLUL	Rebecca Foulger reviewed gene: GLUL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GLUD1	Rebecca Foulger reviewed gene: GLUD1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GLDC	Rebecca Foulger reviewed gene: GLDC: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GLB1	Rebecca Foulger reviewed gene: GLB1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GFM1	Rebecca Foulger reviewed gene: GFM1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GFAP	Rebecca Foulger reviewed gene: GFAP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GCH1	Rebecca Foulger reviewed gene: GCH1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GBA	Rebecca Foulger reviewed gene: GBA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GAMT	Rebecca Foulger reviewed gene: GAMT: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GALC	Rebecca Foulger reviewed gene: GALC: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GABRB2	Rebecca Foulger reviewed gene: GABRB2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	FUT8	Rebecca Foulger reviewed gene: FUT8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	FUCA1	Rebecca Foulger reviewed gene: FUCA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	FRRS1L	Rebecca Foulger reviewed gene: FRRS1L: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	FOLR1	Rebecca Foulger reviewed gene: FOLR1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	FLNA	Rebecca Foulger edited their review of gene: FLNA: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	FKTN	Rebecca Foulger reviewed gene: FKTN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	FH	Rebecca Foulger reviewed gene: FH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	FGFR3	Rebecca Foulger edited their review of gene: FGFR3: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	FGF12	Rebecca Foulger reviewed gene: FGF12: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	FBXO11	Rebecca Foulger reviewed gene: FBXO11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	FBXL4	Rebecca Foulger reviewed gene: FBXL4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	FARS2	Rebecca Foulger edited their review of gene: FARS2: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	FAR1	Rebecca Foulger reviewed gene: FAR1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	EXOSC3	Rebecca Foulger edited their review of gene: EXOSC3: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ETHE1	Rebecca Foulger edited their review of gene: ETHE1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	EMX2	Rebecca Foulger edited their review of gene: EMX2: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Amber.; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	EIF3F	Rebecca Foulger reviewed gene: EIF3F: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	EIF2S3	Rebecca Foulger edited their review of gene: EIF2S3: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	EIF2B5	Rebecca Foulger reviewed gene: EIF2B5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	EIF2B4	Rebecca Foulger edited their review of gene: EIF2B4: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	EIF2B2	Rebecca Foulger edited their review of gene: EIF2B2: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	EFTUD2	Rebecca Foulger reviewed gene: EFTUD2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	EEF1A2	Rebecca Foulger reviewed gene: EEF1A2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	EARS2	Rebecca Foulger edited their review of gene: EARS2: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DYNC1H1	Rebecca Foulger edited their review of gene: DYNC1H1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DPM1	Rebecca Foulger edited their review of gene: DPM1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DPAGT1	Rebecca Foulger edited their review of gene: DPAGT1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DNM1L	Rebecca Foulger edited their review of gene: DNM1L: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DHX30	Rebecca Foulger reviewed gene: DHX30: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DHDDS	Rebecca Foulger edited their review of gene: DHDDS: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DHCR7	Rebecca Foulger edited their review of gene: DHCR7: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DENND5A	Rebecca Foulger edited their review of gene: DENND5A: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DEAF1	Rebecca Foulger edited their review of gene: DEAF1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DDX3X	Rebecca Foulger edited their review of gene: DDX3X: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DCX	Rebecca Foulger reviewed gene: DCX: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	D2HGDH	Rebecca Foulger edited their review of gene: D2HGDH: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CTSD	Rebecca Foulger edited their review of gene: CTSD: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CSTB	Rebecca Foulger reviewed gene: CSTB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CREBBP	Rebecca Foulger reviewed gene: CREBBP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	COQ9	Rebecca Foulger reviewed gene: COQ9: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	COQ4	Rebecca Foulger reviewed gene: COQ4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	COQ2	Rebecca Foulger reviewed gene: COQ2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	COL4A2	Rebecca Foulger reviewed gene: COL4A2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	COL4A1	Rebecca Foulger reviewed gene: COL4A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	COL18A1	Rebecca Foulger reviewed gene: COL18A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	COG7	Rebecca Foulger reviewed gene: COG7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CNNM2	Rebecca Foulger reviewed gene: CNNM2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CLN3	Rebecca Foulger reviewed gene: CLN3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CLCN4	Rebecca Foulger edited their review of gene: CLCN4: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CC2D2A	Rebecca Foulger reviewed gene: CC2D2A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CASK	Rebecca Foulger reviewed gene: CASK: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CAD	Rebecca Foulger edited their review of gene: CAD: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CACNA1G	Rebecca Foulger reviewed gene: CACNA1G: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CACNA1E	Rebecca Foulger reviewed gene: CACNA1E: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CACNA1A	Rebecca Foulger edited their review of gene: CACNA1A: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	C12orf57	Rebecca Foulger reviewed gene: C12orf57: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	BTD	Rebecca Foulger reviewed gene: BTD: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	BRAF	Rebecca Foulger reviewed gene: BRAF: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	BOLA3	Rebecca Foulger reviewed gene: BOLA3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	BCS1L	Rebecca Foulger reviewed gene: BCS1L: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	BCKDHB	Rebecca Foulger reviewed gene: BCKDHB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	BCKDHA	Rebecca Foulger reviewed gene: BCKDHA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ATP7A	Rebecca Foulger reviewed gene: ATP7A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ATP6V1A	Rebecca Foulger reviewed gene: ATP6V1A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ATP1A1	Rebecca Foulger reviewed gene: ATP1A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ASPA	Rebecca Foulger reviewed gene: ASPA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ARV1	Rebecca Foulger reviewed gene: ARV1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ARID1B	Rebecca Foulger reviewed gene: ARID1B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ARG1	Rebecca Foulger reviewed gene: ARG1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ARFGEF2	Rebecca Foulger reviewed gene: ARFGEF2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	AP3B2	Rebecca Foulger reviewed gene: AP3B2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	AMT	Rebecca Foulger reviewed gene: AMT: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	AMPD2	Rebecca Foulger reviewed gene: AMPD2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ALPL	Rebecca Foulger edited their review of gene: ALPL: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ALG9	Rebecca Foulger reviewed gene: ALG9: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ALG8	Rebecca Foulger reviewed gene: ALG8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ALG6	Rebecca Foulger reviewed gene: ALG6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ALG3	Rebecca Foulger reviewed gene: ALG3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ALG1	Rebecca Foulger reviewed gene: ALG1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ALDH5A1	Rebecca Foulger reviewed gene: ALDH5A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	AKT3	Rebecca Foulger reviewed gene: AKT3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	AKT1	Rebecca Foulger reviewed gene: AKT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	AIMP1	Rebecca Foulger edited their review of gene: AIMP1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ADPRHL2	Rebecca Foulger reviewed gene: ADPRHL2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ADGRG1	Rebecca Foulger reviewed gene: ADGRG1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ADAR	Rebecca Foulger reviewed gene: ADAR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ACOX1	Rebecca Foulger reviewed gene: ACOX1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ABAT	Rebecca Foulger reviewed gene: ABAT: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ZEB2	Rebecca Foulger reviewed gene: ZEB2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	WWOX	Rebecca Foulger reviewed gene: WWOX: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	WDR45B	Rebecca Foulger edited their review of gene: WDR45B: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	WDR45	Rebecca Foulger reviewed gene: WDR45: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	UBE3A	Rebecca Foulger reviewed gene: UBE3A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	UBE2A	Rebecca Foulger reviewed gene: UBE2A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TRPM6	Rebecca Foulger reviewed gene: TRPM6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TRAK1	Rebecca Foulger reviewed gene: TRAK1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TPP1	Rebecca Foulger reviewed gene: TPP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TCF4	Rebecca Foulger reviewed gene: TCF4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	TBC1D24	Rebecca Foulger reviewed gene: TBC1D24: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SZT2	Rebecca Foulger edited their review of gene: SZT2: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SYNJ1	Rebecca Foulger edited their review of gene: SYNJ1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SYNGAP1	Rebecca Foulger reviewed gene: SYNGAP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SUOX	Rebecca Foulger reviewed gene: SUOX: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	STXBP1	Rebecca Foulger reviewed gene: STXBP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	STX1B	Rebecca Foulger reviewed gene: STX1B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	STRADA	Rebecca Foulger reviewed gene: STRADA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SPTAN1	Rebecca Foulger reviewed gene: SPTAN1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SLC9A6	Rebecca Foulger edited their review of gene: SLC9A6: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SLC6A19	Rebecca Foulger reviewed gene: SLC6A19: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SLC6A1	Rebecca Foulger reviewed gene: SLC6A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SLC35A2	Rebecca Foulger edited their review of gene: SLC35A2: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SLC2A1	Rebecca Foulger reviewed gene: SLC2A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SLC25A22	Rebecca Foulger reviewed gene: SLC25A22: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SLC25A1	Rebecca Foulger reviewed gene: SLC25A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SLC1A2	Rebecca Foulger reviewed gene: SLC1A2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SLC16A2	Rebecca Foulger reviewed gene: SLC16A2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SLC13A5	Rebecca Foulger reviewed gene: SLC13A5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SLC12A5	Rebecca Foulger reviewed gene: SLC12A5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SIK1	Rebecca Foulger reviewed gene: SIK1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SETD5	Rebecca Foulger reviewed gene: SETD5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SCN9A	Rebecca Foulger reviewed gene: SCN9A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SCN8A	Rebecca Foulger reviewed gene: SCN8A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SCN2A	Rebecca Foulger reviewed gene: SCN2A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SCN1B	Rebecca Foulger reviewed gene: SCN1B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SCN1A	Rebecca Foulger reviewed gene: SCN1A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	SCARB2	Rebecca Foulger reviewed gene: SCARB2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	RANBP2	Rebecca Foulger edited their review of gene: RANBP2: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	QARS	Rebecca Foulger reviewed gene: QARS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PURA	Rebecca Foulger reviewed gene: PURA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PRRT2	Rebecca Foulger reviewed gene: PRRT2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PRODH	Rebecca Foulger reviewed gene: PRODH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	POLG	Rebecca Foulger reviewed gene: POLG: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PNPO	Rebecca Foulger reviewed gene: PNPO: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PNKP	Rebecca Foulger reviewed gene: PNKP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PLPBP	Rebecca Foulger reviewed gene: PLPBP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PLCB1	Rebecca Foulger reviewed gene: PLCB1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PIGT	Rebecca Foulger reviewed gene: PIGT: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PIGN	Rebecca Foulger reviewed gene: PIGN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PIGA	Rebecca Foulger reviewed gene: PIGA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	PCDH19	Rebecca Foulger reviewed gene: PCDH19: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NEXMIF	Rebecca Foulger edited their review of gene: NEXMIF: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	NACC1	Rebecca Foulger edited their review of gene: NACC1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MTOR	Rebecca Foulger reviewed gene: MTOR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MOGS	Rebecca Foulger reviewed gene: MOGS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MFF	Rebecca Foulger reviewed gene: MFF: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MEF2C	Rebecca Foulger reviewed gene: MEF2C: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MECP2	Rebecca Foulger reviewed gene: MECP2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MDH2	Rebecca Foulger reviewed gene: MDH2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MBOAT7	Rebecca Foulger reviewed gene: MBOAT7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	MBD5	Rebecca Foulger reviewed gene: MBD5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	LGI1	Rebecca Foulger reviewed gene: LGI1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KIF1BP	Rebecca Foulger edited their review of gene: KIF1BP: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Amber. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KCTD7	Rebecca Foulger reviewed gene: KCTD7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KCNT1	Rebecca Foulger reviewed gene: KCNT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KCNQ3	Rebecca Foulger reviewed gene: KCNQ3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KCNQ2	Rebecca Foulger reviewed gene: KCNQ2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KCNJ10	Rebecca Foulger reviewed gene: KCNJ10: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KCNC1	Rebecca Foulger reviewed gene: KCNC1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KCNB1	Rebecca Foulger reviewed gene: KCNB1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	KCNA2	Rebecca Foulger reviewed gene: KCNA2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ITPA	Rebecca Foulger reviewed gene: ITPA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	IQSEC2	Rebecca Foulger reviewed gene: IQSEC2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	IER3IP1	Rebecca Foulger reviewed gene: IER3IP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	IDH2	Rebecca Foulger reviewed gene: IDH2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	HTRA2	Rebecca Foulger reviewed gene: HTRA2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	HNRNPU	Rebecca Foulger edited their review of gene: HNRNPU: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	HNRNPH2	Rebecca Foulger reviewed gene: HNRNPH2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	HMGCL	Rebecca Foulger reviewed gene: HMGCL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	HECW2	Rebecca Foulger reviewed gene: HECW2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	HCN1	Rebecca Foulger reviewed gene: HCN1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GSS	Rebecca Foulger reviewed gene: GSS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GRIN2B	Rebecca Foulger reviewed gene: GRIN2B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GRIN2A	Rebecca Foulger reviewed gene: GRIN2A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GRIN1	Rebecca Foulger reviewed gene: GRIN1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GPAA1	Rebecca Foulger reviewed gene: GPAA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GNAO1	Rebecca Foulger reviewed gene: GNAO1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GLYCTK	Rebecca Foulger reviewed gene: GLYCTK: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GABRG2	Rebecca Foulger reviewed gene: GABRG2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GABRB3	Rebecca Foulger reviewed gene: GABRB3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GABRA1	Rebecca Foulger reviewed gene: GABRA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	GABBR2	Rebecca Foulger reviewed gene: GABBR2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	FOXG1	Rebecca Foulger reviewed gene: FOXG1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	EPM2A	Rebecca Foulger reviewed gene: EPM2A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	EPG5	Rebecca Foulger reviewed gene: EPG5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	EML1	Rebecca Foulger edited their review of gene: EML1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	EHMT1	Rebecca Foulger reviewed gene: EHMT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DYRK1A	Rebecca Foulger reviewed gene: DYRK1A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DPYD	Rebecca Foulger reviewed gene: DPYD: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DOCK7	Rebecca Foulger reviewed gene: DOCK7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DNM1	Rebecca Foulger reviewed gene: DNM1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DIAPH1	Rebecca Foulger edited their review of gene: DIAPH1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	DEPDC5	Rebecca Foulger reviewed gene: DEPDC5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CYFIP2	Rebecca Foulger reviewed gene: CYFIP2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CPA6	Rebecca Foulger edited their review of gene: CPA6: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CNTNAP2	Rebecca Foulger reviewed gene: CNTNAP2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CNKSR2	Rebecca Foulger edited their review of gene: CNKSR2: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CLTC	Rebecca Foulger reviewed gene: CLTC: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CLN8	Rebecca Foulger reviewed gene: CLN8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CIC	Rebecca Foulger reviewed gene: CIC: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CHRNB2	Rebecca Foulger reviewed gene: CHRNB2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CHRNA4	Rebecca Foulger reviewed gene: CHRNA4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CHRNA2	Rebecca Foulger reviewed gene: CHRNA2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CHD2	Rebecca Foulger reviewed gene: CHD2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CDKL5	Rebecca Foulger reviewed gene: CDKL5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	CACNA1D	Rebecca Foulger edited their review of gene: CACNA1D: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	BSCL2	Rebecca Foulger reviewed gene: BSCL2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	BRAT1	Rebecca Foulger reviewed gene: BRAT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ATRX	Rebecca Foulger edited their review of gene: ATRX: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ATP6V0A2	Rebecca Foulger reviewed gene: ATP6V0A2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ATP1A3	Rebecca Foulger reviewed gene: ATP1A3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ARX	Rebecca Foulger reviewed gene: ARX: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ARHGEF9	Rebecca Foulger reviewed gene: ARHGEF9: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ALG13	Rebecca Foulger reviewed gene: ALG13: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ALG11	Rebecca Foulger reviewed gene: ALG11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ALDH7A1	Rebecca Foulger reviewed gene: ALDH7A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	ADSL	Rebecca Foulger reviewed gene: ADSL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.189	AARS	Rebecca Foulger reviewed gene: AARS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
06 Aug 2019	Early onset or syndromic epilepsy v1.188	ZIC2	Tracy Lester reviewed gene: ZIC2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Holoprosencephaly 5, 609637; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	TGIF1	Tracy Lester reviewed gene: TGIF1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Holoprosencephaly 4, 142946; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	STIL	Tracy Lester reviewed gene: STIL: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Microcephaly 7, primary, 612703; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	SLC25A19	Tracy Lester reviewed gene: SLC25A19: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Microcephaly, Amish type, 607196 , Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type), 613710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	PTCH1	Tracy Lester reviewed gene: PTCH1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Basal cell carcinoma, somatic, 605462 , Basal cell nevus syndrome, 109400 , Holoprosencephaly 7, 610828; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	PRDM8	Tracy Lester reviewed gene: PRDM8: Rating: RED; Mode of pathogenicity: ; Publications: 22961547; Phenotypes: ?Epilepsy, progressive myoclonic, 10, 616640; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	LMNB2	Tracy Lester reviewed gene: LMNB2: Rating: RED; Mode of pathogenicity: ; Publications: 16826530; Phenotypes: ?Epilepsy, progressive myoclonic, 9, 616540 , {Lipodystrophy, partial, acquired, susceptibility to}, 608709; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	GUF1	Tracy Lester reviewed gene: GUF1: Rating: AMBER; Mode of pathogenicity: ; Publications: 26486472; Phenotypes: ?Epileptic encephalopathy, early infantile, 40, 617065; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	GABRB1	Tracy Lester reviewed gene: GABRB1: Rating: AMBER; Mode of pathogenicity: ; Publications: 27273810, 26950270 ; Phenotypes: Epileptic encephalopathy, early infantile, 45, 617153; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	CUL4B	Tracy Lester reviewed gene: CUL4B: Rating: GREEN; Mode of pathogenicity: ; Publications: 22182342, 17236139 ; Phenotypes: Mental retardation, X-linked, syndromic 15 (Cabezas type), 300354; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
06 Aug 2019	Early onset or syndromic epilepsy v1.188	CTSF	Tracy Lester reviewed gene: CTSF: Rating: AMBER; Mode of pathogenicity: ; Publications: 16508006; Phenotypes: Ceroid lipofuscinosis, neuronal, 13, Kufs type, 615362; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	CERS1	Tracy Lester reviewed gene: CERS1: Rating: AMBER; Mode of pathogenicity: ; Publications: 19243074; Phenotypes: ?Epilepsy, progressive myoclonic, 8, 616230; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	ADRA2B	Tracy Lester reviewed gene: ADRA2B: Rating: AMBER; Mode of pathogenicity: ; Publications: 11701600; Phenotypes: Epilepsy, myoclonic, familial adult, 2, 607876; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	TUBA3E	Tracy Lester reviewed gene: TUBA3E: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Unkown; Mode of inheritance: Unknown
06 Aug 2019	Early onset or syndromic epilepsy v1.188	SLC6A5	Tracy Lester reviewed gene: SLC6A5: Rating: AMBER; Mode of pathogenicity: ; Publications: 16751771, 16884688 ; Phenotypes: Hyperekplexia 3, 614618 ; Mode of inheritance: Unknown
06 Aug 2019	Early onset or syndromic epilepsy v1.188	SHH	Tracy Lester reviewed gene: SHH: Rating: AMBER; Mode of pathogenicity: ; Publications: 8896572; Phenotypes: Holoprosencephaly 3, 142945 , Microphthalmia with coloboma 5, 611638 , Schizencephaly, 269160 , Single median maxillary central incisor, 147250 ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	SEC24D	Tracy Lester reviewed gene: SEC24D: Rating: RED; Mode of pathogenicity: ; Publications: 25363768; Phenotypes: Cole-Carpenter syndrome 2, 616294 ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	SCN2B	Tracy Lester reviewed gene: SCN2B: Rating: RED; Mode of pathogenicity: ; Publications: 12481039, 19808477 ; Phenotypes: Atrial fibrillation, familial, 14, 615378 ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	RYR3	Tracy Lester reviewed gene: RYR3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Unkown; Mode of inheritance: Unknown
06 Aug 2019	Early onset or syndromic epilepsy v1.188	RUBCN	Tracy Lester reviewed gene: RUBCN: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ?Spinocerebellar ataxia 15, 615705 ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	PSMB8	Tracy Lester reviewed gene: PSMB8: Rating: RED; Mode of pathogenicity: ; Publications: 11669176; Phenotypes: Proteasome-associated autoinflammatory syndrome 1 and digenic forms, 256040 ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	PRICKLE2	Tracy Lester reviewed gene: PRICKLE2: Rating: AMBER; Mode of pathogenicity: ; Publications: 21276947; Phenotypes: Seizures; Mode of inheritance: Unknown
06 Aug 2019	Early onset or syndromic epilepsy v1.188	PCDHB4	Tracy Lester reviewed gene: PCDHB4: Rating: RED; Mode of pathogenicity: ; Publications: 22495309; Phenotypes: autism spectrum disorders (ASD) ; Mode of inheritance: Unknown
06 Aug 2019	Early onset or syndromic epilepsy v1.188	NRAS	Tracy Lester reviewed gene: NRAS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Colorectal cancer, somatic, 114500, Epidermal nevus, somatic, 162900, Melanocytic nevus syndrome, congenital, somatic, 137550 , Neurocutaneous melanosis, somatic, 249400 , Noonan syndrome 6, 613224 , ?RAS-associated autoimmune lymphoproliferative syndrome type IV, somatic, 614470 , Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic, 163200 , Thyroid carcinoma, follicular, somatic, 188470 ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	NID1	Tracy Lester reviewed gene: NID1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Unkown; Mode of inheritance: Unknown
06 Aug 2019	Early onset or syndromic epilepsy v1.188	NDUFA11	Tracy Lester reviewed gene: NDUFA11: Rating: AMBER; Mode of pathogenicity: ; Publications: 18306244; Phenotypes: Mitochondrial complex I deficiency, nuclear type 14, 618236 ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	MT-TL1	Tracy Lester reviewed gene: MT-TL1: Rating: RED; Mode of pathogenicity: ; Publications: 1323207; Phenotypes: Myoclonic epilepsy with ragged-red fibers (MERRF); Mode of inheritance: MITOCHONDRIAL
06 Aug 2019	Early onset or syndromic epilepsy v1.188	MATN4	Tracy Lester reviewed gene: MATN4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Developmental delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	MAPK10	Tracy Lester reviewed gene: MAPK10: Rating: RED; Mode of pathogenicity: ; Publications: 16249883, 23329067 ; Phenotypes: epileptic encephalopathy; Mode of inheritance: Unknown
06 Aug 2019	Early onset or syndromic epilepsy v1.188	KAT5	Tracy Lester reviewed gene: KAT5: Rating: RED; Mode of pathogenicity: ; Publications: 28213671, 28195569 ; Phenotypes: Smith-Magenis-like syndrome, schizophrenia; Mode of inheritance: Unknown
06 Aug 2019	Early onset or syndromic epilepsy v1.188	INO80	Tracy Lester reviewed gene: INO80: Rating: RED; Mode of pathogenicity: ; Publications: 24463507; Phenotypes: schizophrenia ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	H3F3B	Tracy Lester reviewed gene: H3F3B: Rating: RED; Mode of pathogenicity: ; Publications: 29529098; Phenotypes: schizophrenia; Mode of inheritance: Unknown
06 Aug 2019	Early onset or syndromic epilepsy v1.188	H3F3A	Tracy Lester reviewed gene: H3F3A: Rating: RED; Mode of pathogenicity: ; Publications: 28506301; Phenotypes: yet to be assigned ; Mode of inheritance: Unknown
06 Aug 2019	Early onset or syndromic epilepsy v1.188	GLRB	Tracy Lester reviewed gene: GLRB: Rating: RED; Mode of pathogenicity: ; Publications: 21391991; Phenotypes: Hyperekplexia 2, 614619 ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	GCSH	Tracy Lester reviewed gene: GCSH: Rating: RED; Mode of pathogenicity: ; Publications: 1671321; Phenotypes: ?Glycine encephalopathy, 605899 ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	GATM	Tracy Lester reviewed gene: GATM: Rating: RED; Mode of pathogenicity: ; Publications: 11555793; Phenotypes: Cerebral creatine deficiency syndrome 3, 612718 ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	GATAD2B	Tracy Lester reviewed gene: GATAD2B: Rating: RED; Mode of pathogenicity: ; Publications: 23033978; Phenotypes: Mental retardation 18, 615074 ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	GAL	Tracy Lester reviewed gene: GAL: Rating: AMBER; Mode of pathogenicity: ; Publications: 21716262, 25691535 ; Phenotypes: ?Epilepsy, familial temporal lobe, 8, 616461 ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	GABRD	Tracy Lester reviewed gene: GABRD: Rating: RED; Mode of pathogenicity: ; Publications: 15115768; Phenotypes: {Epilepsy, generalized, with febrile seizures plus, type 5, susceptibility to}, 613060 , {Epilepsy, idiopathic generalized, 10}, 613060 , {Epilepsy, juvenile myoclonic, susceptibility to}, 613060 ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	FTL	Tracy Lester reviewed gene: FTL: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Hyperferritinemia-cataract syndrome, 600886 , L-ferritin deficiency, dominant and recessive, 615604 , Neurodegeneration with brain iron accumulation 3, 606159 ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	FIG4	Tracy Lester reviewed gene: FIG4: Rating: AMBER; Mode of pathogenicity: ; Publications: 24598713; Phenotypes: Amyotrophic lateral sclerosis 11, 612577, Charcot-Marie-Tooth disease, type 4J, 611228, ?Polymicrogyria, bilateral temporooccipital, 612691, Yunis-Varon syndrome, 216340; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	DMBX1	Tracy Lester reviewed gene: DMBX1: Rating: AMBER; Mode of pathogenicity: ; Publications: 25558065; Phenotypes: global developmental delay, epilepsy and poor weight gain ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	CYP27A1	Tracy Lester reviewed gene: CYP27A1: Rating: AMBER; Mode of pathogenicity: ; Publications: 2019602 , 22336472 ; Phenotypes: Cerebrotendinous xanthomatosis, 213700 ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	CSNK1G1	Tracy Lester reviewed gene: CSNK1G1: Rating: RED; Mode of pathogenicity: ; Publications: 24463883; Phenotypes: severe early-onset epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	CRH	Tracy Lester reviewed gene: CRH: Rating: RED; Mode of pathogenicity: ; Publications: 16222669; Phenotypes: Frontal lobe epilepsy; Mode of inheritance: Unknown
06 Aug 2019	Early onset or syndromic epilepsy v1.188	CNTN2	Tracy Lester reviewed gene: CNTN2: Rating: AMBER; Mode of pathogenicity: ; Publications: 23518707; Phenotypes: ?Epilepsy, myoclonic, familial adult, 5, 615400 ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	CLN6	Tracy Lester reviewed gene: CLN6: Rating: AMBER; Mode of pathogenicity: ; Publications: 21549341; Phenotypes: Ceroid lipofuscinosis neuronal, 6, 601780, Ceroid lipofuscinosis, neuronal Kufs type adult onset, 204300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	CLN5	Tracy Lester reviewed gene: CLN5: Rating: AMBER; Mode of pathogenicity: ; Publications: 9662406; Phenotypes: Ceroid lipofuscinosis, neuronal, 5, 256731 ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	CLCN2	Tracy Lester reviewed gene: CLCN2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: {Epilepsy, idiopathic generalized, susceptibility to, 11}, 607628, {Epilepsy, juvenile absence, susceptibility to, 2}, 607628, {Epilepsy, juvenile myoclonic, susceptibility to, 8}, 607628, Hyperaldosteronism, familial, type II, 605635, Leukoencephalopathy with ataxia, 615651; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	CBL	Tracy Lester reviewed gene: CBL: Rating: AMBER; Mode of pathogenicity: ; Publications: 7603564; Phenotypes: ?Juvenile myelomonocytic leukemia, 607785, Somatic mutation, Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia, 613563 ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	CASR	Tracy Lester reviewed gene: CASR: Rating: RED; Mode of pathogenicity: ; Publications: 7916660; Phenotypes: {Epilepsy idiopathic generalized susceptibility to, 8}, 612899, Hyperparathyroidis, neonatal, 239200, Hypocalcemia, 601198, Hypocalcemia with Bartter syndrome, 601198, Hypocalciuric hypercalcemia type I, 145980; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	CAMK2G	Tracy Lester reviewed gene: CAMK2G: Rating: AMBER; Mode of pathogenicity: ; Publications: 23033978; Phenotypes: intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	CACNB4	Tracy Lester reviewed gene: CACNB4: Rating: AMBER; Mode of pathogenicity: ; Publications: 10762541; Phenotypes: {Epilepsy, idiopathic generalized, susceptibility to, 9}, 607682, {Epilepsy, juvenile myoclonic, susceptibility to, 6}, 607682, Episodic ataxia, type 5, 613855; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	ASAH1	Tracy Lester reviewed gene: ASAH1: Rating: GREEN; Mode of pathogenicity: ; Publications: 8955159, 22703880, 27026573 ; Phenotypes: Farber lipogranulomatosis, 228000, Spinal muscular atrophy with progressive myoclonic epilepsy, 159950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	ALG2	Tracy Lester reviewed gene: ALG2: Rating: RED; Mode of pathogenicity: ; Publications: 12684507; Phenotypes: ?Congenital disorder of glycosylation type Ii, 607906, Myasthenic syndrome congenital 14 with tubular aggregates, 616228; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	ALG12	Tracy Lester reviewed gene: ALG12: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Congenital disorder of glycosylation type Ig, 607143; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	ADGRV1	Tracy Lester reviewed gene: ADGRV1: Rating: AMBER; Mode of pathogenicity: ; Publications: 12402266, 29266188 ; Phenotypes: ?Febrile seizures, familial, 4, 604352 , Usher syndrome, type 2C, 605472 , Usher syndrome, type 2C, GPR98/PDZD7 digenic, 605472; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	AARS2	Tracy Lester reviewed gene: AARS2: Rating: AMBER; Mode of pathogenicity: ; Publications: 21549344, 25817015; Phenotypes: Combined oxidative phosphorylation deficiency 8, 614096, Leukoencephalopathy progressive with ovarian failure, 615889; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	VLDLR	Tracy Lester reviewed gene: VLDLR: Rating: AMBER; Mode of pathogenicity: ; Publications: 19332571, 18326629; Phenotypes: Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1, 224050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	UFC1	Tracy Lester reviewed gene: UFC1: Rating: AMBER; Mode of pathogenicity: ; Publications: 27431290; Phenotypes: Neurodevelopmental disorder with spasticity and poor growth, 618076; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	TXNRD1	Tracy Lester reviewed gene: TXNRD1: Rating: AMBER; Mode of pathogenicity: ; Publications: 28232204; Phenotypes: generalized epilepsy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	TUBB	Tracy Lester reviewed gene: TUBB: Rating: AMBER; Mode of pathogenicity: ; Publications: 23246003; Phenotypes: Cortical dysplasia complex with other brain malformations 6, 615771, Symmetric circumferential skin creases congenital 1, 156610; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	TUBA8	Tracy Lester reviewed gene: TUBA8: Rating: AMBER; Mode of pathogenicity: ; Publications: 19896110; Phenotypes: Cortical dysplasia complex with other brain malformations 8, 613180; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	TSFM	Tracy Lester reviewed gene: TSFM: Rating: AMBER; Mode of pathogenicity: ; Publications: 17033963; Phenotypes: Combined oxidative phosphorylation deficiency 3, 610505; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	TSEN34	Tracy Lester reviewed gene: TSEN34: Rating: AMBER; Mode of pathogenicity: ; Publications: 18711368; Phenotypes: ?Pontocerebellar hypoplasia type 2C, 612390; Mode of inheritance: Unknown
06 Aug 2019	Early onset or syndromic epilepsy v1.188	TSEN15	Tracy Lester reviewed gene: TSEN15: Rating: AMBER; Mode of pathogenicity: ; Publications: 25558065; Phenotypes: Pontocerebellar hypoplasia, type 2F, 617026; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	TRIP13	Tracy Lester reviewed gene: TRIP13: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Mosaic variegated aneuploidy syndrome 3, 617598; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	TRAPPC6B	Tracy Lester reviewed gene: TRAPPC6B: Rating: GREEN; Mode of pathogenicity: ; Publications: 28626029; Phenotypes: Neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy, 617862; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	TRAPPC12	Tracy Lester reviewed gene: TRAPPC12: Rating: GREEN; Mode of pathogenicity: ; Publications: 28777934; Phenotypes: Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, 617669; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	TRAF7	Tracy Lester reviewed gene: TRAF7: Rating: GREEN; Mode of pathogenicity: ; Publications: 29961569; Phenotypes: Cardiac, facial, and digital anomalies with developmental delay, 618164; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	TNK2	Tracy Lester reviewed gene: TNK2: Rating: AMBER; Mode of pathogenicity: ; Publications: 23686771; Phenotypes: autosomal recessive infantile onset epilepsy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	TIMM50	Tracy Lester reviewed gene: TIMM50: Rating: AMBER; Mode of pathogenicity: ; Publications: 27573165; Phenotypes: 3-methylglutaconic aciduria, type IX, 617698; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	TFE3	Tracy Lester reviewed gene: TFE3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Renal cell carcinoma, papillary, 300854; Mode of inheritance: Unknown
06 Aug 2019	Early onset or syndromic epilepsy v1.188	TELO2	Tracy Lester reviewed gene: TELO2: Rating: AMBER; Mode of pathogenicity: ; Publications: 28944240; Phenotypes: You-Hoover-Fong syndrome, 616954; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	TBC1D20	Tracy Lester reviewed gene: TBC1D20: Rating: AMBER; Mode of pathogenicity: ; Publications: 25476608; Phenotypes: Warburg micro syndrome 4, 615663; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	SUCLG1	Tracy Lester reviewed gene: SUCLG1: Rating: AMBER; Mode of pathogenicity: ; Publications: 26028457; Phenotypes: Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria), 245400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	ST3GAL3	Tracy Lester reviewed gene: ST3GAL3: Rating: AMBER; Mode of pathogenicity: ; Publications: 21907012; Phenotypes: ?Epileptic encephalopathy, early infantile, 15, 615006 , Mental retardation 12, 611090 ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	SRPX2	Tracy Lester reviewed gene: SRPX2: Rating: RED; Mode of pathogenicity: ; Publications: 23933820, 23831613 ; Phenotypes: ?Rolandic epilepsy mental retardation and speech dyspraxia, 300643; Mode of inheritance: Unknown
06 Aug 2019	Early onset or syndromic epilepsy v1.188	SPR	Tracy Lester reviewed gene: SPR: Rating: AMBER; Mode of pathogenicity: ; Publications: 11443547; Phenotypes: Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, 612716; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	SNIP1	Tracy Lester reviewed gene: SNIP1: Rating: AMBER; Mode of pathogenicity: ; Publications: 22279524; Phenotypes: Psychomotor retardation, epilepsy, and craniofacial dysmorphism, 614501; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	SMC1A	Tracy Lester reviewed gene: SMC1A: Rating: GREEN; Mode of pathogenicity: ; Publications: 28166369; Phenotypes: Cornelia de Lange syndrome 2, 300590; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
06 Aug 2019	Early onset or syndromic epilepsy v1.188	SLC45A1	Tracy Lester reviewed gene: SLC45A1: Rating: AMBER; Mode of pathogenicity: ; Publications: 28434495; Phenotypes: Intellectual developmental disorder with neuropsychiatric features, 617532; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	SLC35A1	Tracy Lester reviewed gene: SLC35A1: Rating: AMBER; Mode of pathogenicity: ; Publications: 28856833; Phenotypes: Congenital disorder of glycosylation type IIf, 603585; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	SIX3	Tracy Lester reviewed gene: SIX3: Rating: AMBER; Mode of pathogenicity: ; Publications: 15523651, 21940735 ; Phenotypes: Holoprosencephaly 2, 157170, Schizencephaly, 269160; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	SETD1B	Tracy Lester reviewed gene: SETD1B: Rating: AMBER; Mode of pathogenicity: ; Publications: 29322246; Phenotypes: Intellectual disability, epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	SDHA	Tracy Lester reviewed gene: SDHA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Cardiomyopathy, dilated, 1GG, 613642 , Leigh syndrome, 256000 , , Mitochondrial, Mitochondrial respiratory chain complex II deficiency, 252011 , Paragangliomas 5, 614165; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	RYR2	Tracy Lester reviewed gene: RYR2: Rating: RED; Mode of pathogenicity: ; Publications: 18483626; Phenotypes: Arrhythmogenic right ventricular dysplasia 2, 600996, Ventricular tachycardia, catecholaminergic polymorphic, 1, 604772; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	RUSC2	Tracy Lester reviewed gene: RUSC2: Rating: AMBER; Mode of pathogenicity: ; Publications: 27612186; Phenotypes: Mental retardation 61, 617773; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	RRM2B	Tracy Lester reviewed gene: RRM2B: Rating: GREEN; Mode of pathogenicity: ; Publications: 17486094, 19138848 ; Phenotypes: Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), 612075, Mitochondrial DNA depletion syndrome 8B (MNGIE type), 612075, Progressive external ophthalmoplegia with mitochondrial DNA deletions 5, 613077; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	RPIA	Tracy Lester reviewed gene: RPIA: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ?Ribose 5-phosphate isomerase deficiency, 608611; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	RNU4ATAC	Tracy Lester reviewed gene: RNU4ATAC: Rating: RED; Mode of pathogenicity: ; Publications: 22581640; Phenotypes: Microcephalic osteodysplastic primordial dwarfism, type I, 210710 , Roifman syndrome, 616651; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	RAB3GAP2	Tracy Lester reviewed gene: RAB3GAP2: Rating: AMBER; Mode of pathogenicity: ; Publications: 20967465; Phenotypes: Martsolf syndrome, 212720 , Warburg micro syndrome 2, 614225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	RAB3GAP1	Tracy Lester reviewed gene: RAB3GAP1: Rating: RED; Mode of pathogenicity: ; Publications: 20512159; Phenotypes: Warburg micro syndrome 1, 600118; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	PTF1A	Tracy Lester reviewed gene: PTF1A: Rating: AMBER; Mode of pathogenicity: ; Publications: 28663161; Phenotypes: Pancreatic agenesis 2, 615935, Pancreatic and cerebellar agenesis, 609069; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	PSPH	Tracy Lester reviewed gene: PSPH: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Phosphoserine phosphatase deficiency, 614023; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	PSAT1	Tracy Lester reviewed gene: PSAT1: Rating: RED; Mode of pathogenicity: ; Publications: 17436247; Phenotypes: Neu-Laxova syndrome 2, 616038 , ?Phosphoserine aminotransferase deficiency, 610992; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	POMT2	Tracy Lester reviewed gene: POMT2: Rating: RED; Mode of pathogenicity: ; Publications: 17878207; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies) type A, 613150, Muscular dystrophy-dystroglycanopathy (congenital with mental retardation) , 613156, Muscular dystrophy-dystroglycanopathy (limb-girdle), 613158; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	PIGQ	Tracy Lester reviewed gene: PIGQ: Rating: GREEN; Mode of pathogenicity: ; Publications: 24463883; Phenotypes: Glycosylphosphatidylinositol biosynthesis defect ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	PIGH	Tracy Lester reviewed gene: PIGH: Rating: GREEN; Mode of pathogenicity: ; Publications: 29573052; Phenotypes: Glycosylphosphatidylinositol biosynthesis defect 17, 618010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	PIGC	Tracy Lester reviewed gene: PIGC: Rating: GREEN; Mode of pathogenicity: ; Publications: 27694521; Phenotypes: Glycosylphosphatidylinositol biosynthesis defect 16, 617816; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	PEX5	Tracy Lester reviewed gene: PEX5: Rating: GREEN; Mode of pathogenicity: ; Publications: 7719337; Phenotypes: Peroxisome biogenesis disorder 2A (Zellweger), 214110 , Peroxisome biogenesis disorder 2B, 202370, Rhizomelic chondrodysplasia punctata type 5, 616716; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	PDSS2	Tracy Lester reviewed gene: PDSS2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Coenzyme Q10 deficiency primary 3, 614652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	PCLO	Tracy Lester reviewed gene: PCLO: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ?Pontocerebellar hypoplasia, type 3, 608027; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	OTX2	Tracy Lester reviewed gene: OTX2: Rating: AMBER; Mode of pathogenicity: ; Publications: 19965921, 15846561 ; Phenotypes: Microphthalmia syndromic 5, 610125, Pituitary hormone deficiency combined, 613986, Retinal dystrophy early-onset with or without pituitary dysfunction, 610125; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	NUBPL	Tracy Lester reviewed gene: NUBPL: Rating: AMBER; Mode of pathogenicity: ; Publications: 20818383; Phenotypes: Mitochondrial complex I deficiency, nuclear type 21, 618242; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	NPRL2	Tracy Lester reviewed gene: NPRL2: Rating: AMBER; Mode of pathogenicity: ; Publications: 26505888; Phenotypes: Epilepsy familial focal with variable foci 2, 617116; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	NEDD4L	Tracy Lester reviewed gene: NEDD4L: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Periventricular nodular heterotopia 7, 617201; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	NECAP1	Tracy Lester reviewed gene: NECAP1: Rating: AMBER; Mode of pathogenicity: ; Publications: 24399846; Phenotypes: ?Epileptic encephalopathy, early infantile, 21, 615833; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	NDUFS7	Tracy Lester reviewed gene: NDUFS7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 3, 618224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	NDUFS6	Tracy Lester reviewed gene: NDUFS6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 9, 618232; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	NDUFS2	Tracy Lester reviewed gene: NDUFS2: Rating: AMBER; Mode of pathogenicity: ; Publications: 20819849; Phenotypes: Mitochondrial complex I deficiency, nuclear type 6, 618228; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	NDUFS1	Tracy Lester reviewed gene: NDUFS1: Rating: AMBER; Mode of pathogenicity: ; Publications: 11349233; Phenotypes: Mitochondrial complex I deficiency, nuclear type 5, 618226; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	NDUFAF4	Tracy Lester reviewed gene: NDUFAF4: Rating: AMBER; Mode of pathogenicity: ; Publications: 19463981, 28853723; Phenotypes: Mitochondrial complex I deficiency, nuclear type 15, 618237; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	NDUFAF3	Tracy Lester reviewed gene: NDUFAF3: Rating: AMBER; Mode of pathogenicity: ; Publications: 19463981; Phenotypes: Mitochondrial complex I deficiency nuclear type 18, 618240; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	NDUFA2	Tracy Lester reviewed gene: NDUFA2: Rating: AMBER; Mode of pathogenicity: ; Publications: 18513682; Phenotypes: ?Mitochondrial complex I deficiency nuclear type 13, 618235; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	NDP	Tracy Lester reviewed gene: NDP: Rating: RED; Mode of pathogenicity: ; Publications: 17334993, 27217716; Phenotypes: Norrie disease, 310600; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
06 Aug 2019	Early onset or syndromic epilepsy v1.188	MED17	Tracy Lester reviewed gene: MED17: Rating: AMBER; Mode of pathogenicity: ; Publications: 20950787; Phenotypes: Microcephaly postnatal progressive with seizures and brain atrophy, 613668; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	MAST1	Tracy Lester reviewed gene: MAST1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations, 618273; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	MANBA	Tracy Lester reviewed gene: MANBA: Rating: AMBER; Mode of pathogenicity: ; Publications: 22369051; Phenotypes: Mannosidosis, beta, 248510; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	LNPK	Tracy Lester reviewed gene: LNPK: Rating: AMBER; Mode of pathogenicity: ; Publications: 30032983; Phenotypes: Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum, 618090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	LIPT2	Tracy Lester reviewed gene: LIPT2: Rating: RED; Mode of pathogenicity: ; Publications: 28757203; Phenotypes: Encephalopathy neonatal severe with lactic acidosis and brain abnormalities, 617668; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	LARGE1	Tracy Lester reviewed gene: LARGE1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies) type A, 613154, Muscular dystrophy-dystroglycanopathy (congenital with mental retardation) type B, 608840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	KPTN	Tracy Lester reviewed gene: KPTN: Rating: AMBER; Mode of pathogenicity: ; Publications: 24239382; Phenotypes: Mental retardation 41, 615637; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	KIAA1109	Tracy Lester reviewed gene: KIAA1109: Rating: GREEN; Mode of pathogenicity: ; Publications: 29290337; Phenotypes: Alkuraya-Kucinskas syndrome, 617822; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	KCNMA1	Tracy Lester reviewed gene: KCNMA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ?Cerebellar atrophy developmental delay and seizures, 617643, Paroxysmal nonkinesigenic dyskinesia 3 with or without generalized epilepsy, 609446; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	ISPD	Tracy Lester reviewed gene: ISPD: Rating: AMBER; Mode of pathogenicity: ; Publications: 15937479, 26195193 ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies) type A, 7 614643, Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 7 616052; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	HSPD1	Tracy Lester reviewed gene: HSPD1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Leukodystrophy hypomyelinating 4, 612233, Spastic paraplegia 13, 605280; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	HPRT1	Tracy Lester reviewed gene: HPRT1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: HPRT-related gout, 300323, Lesch-Nyhan syndrome, 300322; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
06 Aug 2019	Early onset or syndromic epilepsy v1.188	HOXA1	Tracy Lester reviewed gene: HOXA1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Athabaskan brainstem dysgenesis syndrome, 601536 , Bosley-Salih-Alorainy syndrome, 601536; Mode of inheritance: Unknown
06 Aug 2019	Early onset or syndromic epilepsy v1.188	HEXB	Tracy Lester reviewed gene: HEXB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Sandhoff disease infantile juvenile and adult forms, 268800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	HCCS	Tracy Lester reviewed gene: HCCS: Rating: RED; Mode of pathogenicity: ; Publications: 17033964; Phenotypes: Linear skin defects with multiple congenital anomalies, 309801; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
06 Aug 2019	Early onset or syndromic epilepsy v1.188	GTPBP3	Tracy Lester reviewed gene: GTPBP3: Rating: GREEN; Mode of pathogenicity: ; Publications: 25434004; Phenotypes: Combined oxidative phosphorylation deficiency 23, 616198; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	GLRA1	Tracy Lester reviewed gene: GLRA1: Rating: AMBER; Mode of pathogenicity: ; Publications: 20631190; Phenotypes: Hyperekplexia 1, 149400; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	GLI3	Tracy Lester reviewed gene: GLI3: Rating: RED; Mode of pathogenicity: ; Publications: 11484201; Phenotypes: Greig cephalopolysyndactyly syndrome, 175700, {Hypothalamic hamartomas, somatic}, 241800 , Pallister-Hall syndrome, 146510, Polydactyly postaxial types A1 and B, 174200, Polydactyly preaxial type IV, 174700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	FOXRED1	Tracy Lester reviewed gene: FOXRED1: Rating: AMBER; Mode of pathogenicity: ; Publications: 20818383, 27215383; Phenotypes: Mitochondrial complex I deficiency nuclear type 19, 618241; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	FKRP	Tracy Lester reviewed gene: FKRP: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies) type A 613153, Muscular dystrophy-dystroglycanopathy (congenital with or without mental retardation) type B, 606612, Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 5, 607155; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	FASTKD2	Tracy Lester reviewed gene: FASTKD2: Rating: AMBER; Mode of pathogenicity: ; Publications: 28499982, 18771761, 25916514 ; Phenotypes: ?Mitochondrial complex IV deficiency, 220110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	EIF2B3	Tracy Lester reviewed gene: EIF2B3: Rating: GREEN; Mode of pathogenicity: ; Publications: 21307862; Phenotypes: Leukoencephalopathy with vanishing white matter, 603896; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	EIF2B1	Tracy Lester reviewed gene: EIF2B1: Rating: GREEN; Mode of pathogenicity: ; Publications: 25843247, 25761052 ; Phenotypes: Leukoencephalopathy with vanishing white matter, 603896; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	EFHC1	Tracy Lester reviewed gene: EFHC1: Rating: GREEN; Mode of pathogenicity: ; Publications: 19901254; Phenotypes: {Epilepsy, juvenile absence, susceptibility to, 1}, 607631 , {Myoclonic epilepsy, juvenile, susceptibility to, 1}, 254770; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
06 Aug 2019	Early onset or syndromic epilepsy v1.188	DPM2	Tracy Lester reviewed gene: DPM2: Rating: GREEN; Mode of pathogenicity: ; Publications: 23109149, 19901254 ; Phenotypes: Congenital disorder of glycosylation type Iu, 615042; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	DOLK	Tracy Lester reviewed gene: DOLK: Rating: AMBER; Mode of pathogenicity: ; Publications: 23890587; Phenotypes: Congenital disorder of glycosylation type Im, 610768; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	DNAJC6	Tracy Lester reviewed gene: DNAJC6: Rating: AMBER; Mode of pathogenicity: ; Publications: 23211418; Phenotypes: Parkinson disease 19a juvenile-onset, 615528, Parkinson disease 19b early-onset, 615528; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	DHCR24	Tracy Lester reviewed gene: DHCR24: Rating: AMBER; Mode of pathogenicity: ; Publications: 21559050, 21671375 ; Phenotypes: Desmosterolosis, 602398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	DBT	Tracy Lester reviewed gene: DBT: Rating: GREEN; Mode of pathogenicity: ; Publications: 1990841; Phenotypes: Maple syrup urine disease,type II 248600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
06 Aug 2019	Early onset or syndromic epilepsy v1.188	CUX2	Tracy Lester reviewed gene: CUX2: Rating: GREEN; Mode of pathogenicity: ; Publications: 29795476, 29630738 ; Phenotypes: Epileptic encephalopathy early infantile 67, 618141; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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