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| Fetal anomalies v3.157 | USP14 |
Zornitza Stark gene: USP14 was added gene: USP14 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: USP14 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: USP14 were set to 38469793 Phenotypes for gene: USP14 were set to Syndromic disease MONDO:0002254, USP14-related Review for gene: USP14 was set to AMBER Added comment: PMID 38469793: biallelic USP14 variants in four individuals from three unrelated families: one fetus, a newborn with a syndromic NDD, and two siblings affected by a progressive neurological disease. Specifically, the two siblings from the latter family carried two compound heterozygous variants c.8T>C p.(Leu3Pro) and c.988C>T p.(Arg330*), while the fetus had a homozygous frameshift c.899_902del p.(Lys300Serfs*24) variant and the newborn patient harbored a homozygous frameshift c.233_236del p.(Leu78Glnfs*11) variant. The fetus and the newborn had extensive brain malformations. Sources: Literature |
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| Fetal anomalies v3.156 | PLD1 |
Arina Puzriakova commented on gene: PLD1: Copied review from Paediatric or syndromic cardiomyopathy (749) v3.43 panel: Jesse Hayesmoore (Oxford Regional Genetics Laboratory) Red List (low evidence) "On the basis of functional data described in PMIDs: 27799408 and 33645542, PLD1 certainly seems to be a plausible functional candidate for causality of cardiac valvular defects. The main paper linking this gene with congenital heart disease / cardiomyopathy is Lahrouchi et al. (2021; PMID: 33645542; note this also includes the same 2 cases as described in Ta-Shma et al. 2017 PMID: 27799408). The paper presents 19 families with severe fetal- / neonatal-onset congenital heart (mainly valvular) defects and 2 with cardiomyopathy where affected babies were homozygous or compound heterozygous for PLD1 variants. The paper also provides some functional analysis of missense variants detected, showing that many but not all of them result significant loss of PLD1 function. Unfortunately, the paper does not include a LOD score, and there is very little cosegregation data presented for any of the variants. In addition, 4 of the 31 variants they promote as pathogenic for autosomal recessive disease are detected in multiple homozygous individuals on gnomAD, which I think provides significant evidence that they might not be pathogenic for a severe autosomal recessive condition. Most notably, 1 of the variants (i.e. I668F), which the authors promote as a pathogenic Ashkenazi Jewish founder variant (but which is also fairly frequent in non-Finnish Europeans) is detected in 7 homozygotes on gnomAD and was found to have ~80% loss of PLD1 function in their assay. This suggests that significant loss of function of this gene (i.e. down to 20%) might not be causative of a severe recessive condition (that is not to say that total or near total loss of function is not causative). Three other of the variants promoted as pathogenic in this article are also detected in homozygotes on gnomAD. I think one of the major pieces of missing information required to make a full assessment of this gene’s linkage to disease is that is unknown how frequent biallelic (apparently loss of function) variant genotypes are in the general population or in healthy control individuals. Although homozygosity for any one variant can be determined from gnomAD, compound heterozygosity (which is likely to represent the vast majority of biallelic genotypes) cannot be assessed on gnomAD, and I can find no record in the literature of this being assessed in a normal control cohort. Without this information, we cannot know whether biallelic PLD1 genotypes are specific to babies with this severe phenotype. Without knowing this, and in the absence of any significant cosegregation data for any variant, there is no reasonable basis upon which one can conclude that this is a valid autosomal recessive gene for the phenotype. Without such validation, PVS1 cannot be applied for any apparent loss of function variant. Given this, and the general lack of cosegregation data for any one variant, I do not believe there is any PLD1 variant reported in the literature that could be classified as anything but uncertain significance (if not benign or likely benign) on the basis of current variant classification guidelines. Also, there are only two cases of biallelic variants in neonates where the primary phenotype is cardiomyopathy, and of these only one was dilated cardiomyopathy (the other was histiocytoid cardiomyopathy). Hence, the evidence linking this gene to cardiomyopathy is even weaker than it is for valvular defects. I, therefore, do not feel there is sufficient evidence to justify this gene being tested as part of the R135 paediatric cardiomyopathy gene panel. Other papers (e.g. PMIDs: 33142350, 35380090, 36923242, 37770978) reporting a link between PLD1 genotypes and early onset cardiac disease (not cardiomyopathy) have been published. However, again, I do not think there is sufficient data in the articles to allow any of the variants detected to be confidently classified as anything but VUS according to current variant classification guidelines." Created: 31 Jan 2024, 12:04 p.m. | Last Modified: 31 Jan 2024, 12:17 p.m |
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| Fetal anomalies v3.151 | RRAS | Sarah Leigh edited their review of gene: RRAS: Added comment: RRAS variants have not associated with a phenotype in OMIM or MONDO, but Gen2Phen lists a strong association between RRAS variants and RRAS-related atypical Noonan syndrome. Three germline RRAS variants have been reported (PMID: 24705357; 32815881; 34935735), associated with a RASopathy, which includes myelodysplastic syndrome and contributes to leukaemogenesis.; Changed rating: GREEN; Changed publications to: 24705357, 32815881, 34935735 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v3.119 | SEC23B | Arina Puzriakova Phenotypes for gene: SEC23B were changed from ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE II to Dyserythropoietic anemia, congenital, type II, OMIM:224100 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v3.116 | ESAM | Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Julia Baptista, PMID:36996813 reported foetal intracranial hemorrhage in four foetuses from three unrelated families. Hence, there is sufficient evidence for this gene to be promoted to green rating in this panel in the next GMS review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v3.109 | ESAM |
Julia Baptista gene: ESAM was added gene: ESAM was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ESAM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ESAM were set to PMID: 36996813 Phenotypes for gene: ESAM were set to intracranial hemorrhage; cerebral anomalies Review for gene: ESAM was set to GREEN Added comment: Four fetuses from three unrelated families (different LOF biallelic variants) with fetal intracranial hemorrhage. Fetal brain tissue from one of the affected individuals at 31 weeks' gestational age showed lack of ESAM staining in the capillary endothelial cells, thus confirming loss of ESAM. Another individual had an abnormal prenatal ultrasound and the pregnancy was terminated at 32 weeks' gestation, but no DNA was available to test for the familial variant. Neurodevelopmental disorder with cerebral calcifications, hydrocephalus, focal white matter lesions, retina anomalies and dysmorphic features. Sources: Literature |
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| Fetal anomalies v3.96 | SLC25A24 | Sarah Leigh Added comment: Comment on phenotypes: Gorlin-Chaudhry-Moss syndrome (GCMS);Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v3.96 | SLC25A24 | Sarah Leigh Phenotypes for gene: SLC25A24 were changed from Gorlin-Chaudhry-Moss syndrome (GCMS); Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction to Fontaine progeroid syndrome, OMIM; 612289; Fontaine progeroid syndrome, MONDO:0012853 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v3.73 | MYL9 | Arina Puzriakova commented on gene: MYL9: Third family reported by Billon et al. 2020 (PMID: 32621347) with the same homozygous exon 4 deletion of MYL9 as the one detected by Moreno et al. 2018 (PMID: 29453416) in an unrelated case. Family includes three sibs affected with megacystis, intestinal malrotation, small and thin colon, as well as some dysmorphic features. Fetopathological examination confirmed the diagnosis of MMIHS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v3.70 | MECOM | Arina Puzriakova Phenotypes for gene: MECOM were changed from Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia; Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, OMIM:616738 to Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, OMIM:616738 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v3.8 | MECOM | Stephanie Allen reviewed gene: MECOM: Rating: GREEN; Mode of pathogenicity: ; Publications: 29540340, 26581901; Phenotypes: Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, OMIM:616738; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v3.7 | MECOM | Arina Puzriakova Added phenotypes Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, OMIM:616738 for gene: MECOM | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v3.2 | KIF21A |
Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to recommend this gene to NHS GMS for promoting to green rating. There are two unrelated families with homozygous loss of function variants in KIF21A were reported with severe fetal akinesia with arthrogryposis multiplex in PMID:34740919. Hannah Robinson (South West Genomic Laboratory Hub) reported an additional case identified in Exeter Genomics Laboratory exhibiting homozygous nonsense variant in KIF21A and was diagnosed with arthrogryposis. In addition, PMID:32686171 reports overlapping phenotypes observed in KIF21A null piglets, where a 63-bp insertion in exon 2 of the porcine KIF21A gene is associated with arthrogryposis multiplex congenita. |
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| Fetal anomalies v2.8 | KIF21A |
Hannah Robinson gene: KIF21A was added gene: KIF21A was added to Fetal anomalies. Sources: Literature,NHS GMS Mode of inheritance for gene: KIF21A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIF21A were set to 34740919 Phenotypes for gene: KIF21A were set to Arthrogryposis; fetal akinesia Penetrance for gene: KIF21A were set to unknown Review for gene: KIF21A was set to GREEN gene: KIF21A was marked as current diagnostic Added comment: Falb et al 2023 (PMID: 34740919) describe two unrelated families in which biallelic loss of function variants segregated with a severe form of fetal akinesia characterised by arthrogryposis multiplex, pulmonary hypoplasia and variable facial dysmorphisms. Exeter Genomics Laboratory has identified an unrelated third case homozygous for a nonsense variant in KIF21A. The patient had an antenatal diagnosis of talipes, arthrogryposis, polyhydramnios and lack of fetal movements. At birth, all joints displayed fixed flexion deformities, no primitive reflexes, poor muscle bulk and care was re-oriented shortly after birth. Taken together, three unrelated cases including segregation evidence in the published families provides sufficient evidence for the gene-disease association. Sources: Literature, NHS GMS |
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| Fetal anomalies v2.3 | CHRNE | Arina Puzriakova Phenotypes for gene: CHRNE were changed from Myasthenic syndrome, congenital, 4A, slow-channel, 605809; Myasthenic syndrome, congenital, 4B, fast-channel, 616324; Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency, 608931 to Myasthenic syndrome, congenital, 4A, slow-channel, OMIM:605809; Myasthenic syndrome, congenital, 4B, fast-channel, OMIM:616324; Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency, OMIM:608931 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.981 | ADAR | Arina Puzriakova Phenotypes for gene: ADAR were changed from DYSCHROMATOSIS SYMMETRICA HEREDITARIA 1; AICARDI-GOUTIERES SYNDROME ASSOCIATED WITH A TYPE I INTERFERON SIGNATURE to Aicardi-Goutieres syndrome 6, OMIM:615010; Dyschromatosis symmetrica hereditaria, OMIM:127400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.926 | CHRM3 | Arina Puzriakova Publications for gene: CHRM3 were set to 22077972; 31441039; 10944224 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.925 | CHRM3 | Arina Puzriakova Classified gene: CHRM3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.925 | CHRM3 | Arina Puzriakova Gene: chrm3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.924 | CHRM3 | Arina Puzriakova Phenotypes for gene: CHRM3 were changed from Prune belly syndrome; Megacystis to Prune belly syndrome, OMIM:100100; Megacystis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.923 | CHRM3 | Arina Puzriakova Publications for gene: CHRM3 were set to PMID: 22077972; 31441039; 10944224 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.914 | ASXL3 | Arina Puzriakova Phenotypes for gene: ASXL3 were changed from BAINBRIDGE-ROPERS SYNDROME to Bainbridge-Ropers syndrome, OMIM:615485; Arthrogryposis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.905 | WNT7B |
Arina Puzriakova Added comment: Comment on list classification: New gene added by Julia Baptista. There is sufficient evidence to promote this gene to Green at the next GMS panel update. Three families reported with fetuses with multiple congenital anomalies (PMID: 35790350). Biallelic variants were identified in probands of two families and parents in third family were both heterozygous for a variant found in one of the other families. Although the fetus was not available for testing, the genotype can be inferred as homozygous for the variant given the consistent phenotype between cases. Supportive zebrafish model supports pathogenicity. |
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| Fetal anomalies v1.900 | CHRM3 |
Rhiannon Mellis gene: CHRM3 was added gene: CHRM3 was added to Fetal anomalies. Sources: Expert Review,Literature Mode of inheritance for gene: CHRM3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CHRM3 were set to PMID: 22077972; 31441039; 10944224 Phenotypes for gene: CHRM3 were set to Prune belly syndrome; Megacystis Review for gene: CHRM3 was set to AMBER Added comment: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH). Outcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene. Details of review: Discussed as a potential cause of megacystis. Currently Red on Panelapp CAKUT panel (2016) because at that time there was only 1 reported family and a mouse model. The unpublished data mentioned in that panelapp review (from Adrian Woolf, Manchester) is now published so now 2 families PMID: 22077972; 31441039 plus a mouse model PMID: 10944224. However, prenatal findings (distended bladder and unilateral hydronephrosis) only documented for one individual. More evidence of prenatal phenotype would be helpful. Sources: Expert Review, Literature |
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| Fetal anomalies v1.900 | PIGS |
Rhiannon Mellis gene: PIGS was added gene: PIGS was added to Fetal anomalies. Sources: Expert Review,Literature Mode of inheritance for gene: PIGS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIGS were set to PMID: 30269814 Phenotypes for gene: PIGS were set to Developmental and epileptic encephalopathy 95 Review for gene: PIGS was set to AMBER Added comment: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH). Outcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene. Details of review: Currently red/amber on some other panels but reviewed on Congenital disorders of glycosylation panel as having sufficient evidence for green rating at next major review, in light of this same paper (PMID: 30269814). Three unrelated families reported. Severe neurological phenotype ranging from fetal akinesia to intellectual disability/epileptic encephalopathy. Fetal akinesia phenotype may be relevant for fetal anomalies panel. Sources: Expert Review, Literature |
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| Fetal anomalies v1.900 | CACNA1S |
Rhiannon Mellis gene: CACNA1S was added gene: CACNA1S was added to Fetal anomalies. Sources: Expert Review,Literature Mode of inheritance for gene: CACNA1S was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CACNA1S were set to PMID: 33060286; 28012042 Phenotypes for gene: CACNA1S were set to Congenital myopathy; arthrogryposis Review for gene: CACNA1S was set to AMBER Added comment: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH). Outcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene. Details of review: Previously only monoallelic variants reported associated with malignant hyperthermia and periodic paralysis but more recently biallelic variants have been associated with congenital myopathy. In Ravenscroft et al 2020 (PMID: 33060286) the reported biallelic variants were VUS but strong suspicion of causality: the proband had polyhydramnios, scalp oedema, bilateral wrist contractures, bilateral talipes and reduced fetal movements, ToP at 26/40. Mild facial dysmorphic features were noted on autopsy, including low anterior hairline, mild hypertelorism and moderate retrognathia. A previous pregnancy was affected with polyhydramnios and reduced fetal movements, delivered at 32/40 due to placental abruption and died at 10 days. On photos the baby had ptosis and broad nasal tip. The biallelic variants segregated within the family (parents and the 2 unaffected sibs all het). No cell lines available for functional studies. Another study (PMID: 28012042) reports 7 families with congenital myopathy and CACNA1S mutations (both recessive and dominant), of whom 3 had cases with antenatal onset (reduced fetal movements). Sources: Expert Review, Literature |
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| Fetal anomalies v1.900 | FTO |
Rhiannon Mellis gene: FTO was added gene: FTO was added to Fetal anomalies. Sources: Expert Review,Literature Mode of inheritance for gene: FTO was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FTO were set to PMID: 31130284; 19559399; 26378117 Phenotypes for gene: FTO were set to Growth retardation, developmental delay, facial dysmorphism Review for gene: FTO was set to AMBER Added comment: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH). Outcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene. Details of review: Not Green on any panels (only 2 families reported to date). On OMIM: Growth retardation, developmental delay, facial dysmorphism. One fetal case reported by Monies et al 2019 (PMID: 31130284) with Dandy-Walker malformation, IUGR, and polyhydramnios. This fits with the phenotype reported in one consanguineous family with 9 affected individuals reported by Boissel 2009 PMID: 19559399. The other reported case is PMID: 26378117 - a homozygous missense variant in FTO was identified in a 21-month old girl who presented with growth retardation, failure to thrive, severely delayed development, Dysmorphic facial features, decreased brain parenchyma, delayed myelination, and a thin corpus callosum. Sources: Expert Review, Literature |
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| Fetal anomalies v1.900 | ASXL3 |
Rhiannon Mellis edited their review of gene: ASXL3: Added comment: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH). Outcome of review: May be fetally relevant but still limited evidence, support keeping as Amber gene for now. Details of review: Previously reviewed as Amber as 2 fetal cases in literature: one from PMID: 32565546 with short CC and metopic synostosis, one from PMID: 29316359 with distal arthrogryposis and cerebellar vermian hypoplasia. Now there is one more fetal case reported with arthrogryposis - PMID: 33820833; Changed publications to: PMID: 33820833; Changed phenotypes to: Arthrogryposis |
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| Fetal anomalies v1.879 | LONP1 | Arina Puzriakova commented on gene: LONP1: Added 'watchlist_moi' tag to monitor recently reported association with congenital diaphragmatic hernia as highlighted in review by Zornitza Stark (Australian Genomics) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.877 | ZFPM2 | Arina Puzriakova Added comment: Comment on list classification: Rating Amber based on the evidence provided in review by Anna de Burca. Gene-disease association is classified with 'limited' confidence in G2P. Cases indicate reduced penetrance and no functional studies of variants relating to diaphragmatic hernia have been reported thus far. Gene is also associated with other phenotypes with limited support. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.876 | ZFPM2 | Arina Puzriakova Phenotypes for gene: ZFPM2 were changed from Congenital diaphragmatic hernia to Diaphragmatic hernia 3, OMIM:610187 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.873 | WNT7B |
Julia Baptista gene: WNT7B was added gene: WNT7B was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: WNT7B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WNT7B were set to 35790350 Phenotypes for gene: WNT7B were set to Pulmonary hypoplasia; Diaphragmatic anomalies; Anophthalmia/Microphthalmia; Cardiac defects Review for gene: WNT7B was set to GREEN Added comment: One homozygous nonsense variant identified in family 1. Compound heterozygous missense and nonsense variants identified in two affected fetuses in family 2. A third family with limited phenotypic information available, with parents heterozygous for the same nonsense variant, p. (Arg98Ter), identified in family 1, but no segregation studies in the affected. Animal studies in Danio rerio were supportive. Lung hypoplasia with tracheal, ocular, cardiac, and renal defects. Sources: Expert Review |
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| Fetal anomalies v1.870 | SRY | Eleanor Williams commented on gene: SRY: Added Y chromosome tag to indicate this gene is encoded on the Y chromosome, which is currently not included in the Bioinformatics tiering pipeline. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.870 | SRY | Eleanor Williams Tag y-chromosome tag was added to gene: SRY. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.864 | ZFPM2 |
Anna de Burca gene: ZFPM2 was added gene: ZFPM2 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ZFPM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZFPM2 were set to 24702427 Phenotypes for gene: ZFPM2 were set to Congenital diaphragmatic hernia Penetrance for gene: ZFPM2 were set to Incomplete Review for gene: ZFPM2 was set to AMBER Added comment: Paper suggests that ZFPM2 variants may be associated with isolated congenital diaphragmatic hernia, but penetrance appears reduced. Given the apparently reduced penetrance and since isolated CDH is a relatively common congenital finding, the gene-disease association remains uncertain. Of note, variants in this gene have also been associated with 46,XY sex reversal and Tetralogy of Fallot. Sources: Literature |
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| Fetal anomalies v1.858 | COL1A2 |
Eleanor Williams changed review comment from: The mode of inheritance for the following phenotypes is monoallelic. - Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 (OMIM:619120) - Ehlers-Danlos syndrome, arthrochalasia type, 2 (OMIM:617821) - Osteogenesis imperfecta, type II (OMIM:166210) - Osteogenesis imperfecta, type III (OMIM:259420) - Osteogenesis imperfecta, type IV (OMIM:166220) Only Ehlers-Danlos syndrome, cardiac valvular type (OMIM: 225320) has a biallelic mode of inheritance.; to: Variants in this gene are associated with the following phenotypes in OMIM with a monoallelic mode of inheritance: - Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 (OMIM:619120) - Ehlers-Danlos syndrome, arthrochalasia type, 2 (OMIM:617821) - Osteogenesis imperfecta, type II (OMIM:166210) - Osteogenesis imperfecta, type III (OMIM:259420) - Osteogenesis imperfecta, type IV (OMIM:166220) Only Ehlers-Danlos syndrome, cardiac valvular type (OMIM: 225320) has a biallelic mode of inheritance. |
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| Fetal anomalies v1.854 | LIFR |
Eleanor Williams changed review comment from: Heterozygous variants in LIFR are associated with a CAKUT phenotype, while homozygous variants are associated with skeletal Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndromes. At the moment the mode of inheritance for this gene on the Fetal anomalies panel is biallelic only. GMS fetal group input is needed to decide whether the mode of inheritance for this gene should also include monoallelic cases as the renal phenotype might be detected antenatally e.g. hydronephrosis.; to: Heterozygous variants in LIFR are associated with a CAKUT phenotype, while homozygous variants are associated with skeletal Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndromes. At the moment the mode of inheritance for this gene on the Fetal anomalies panel is biallelic only. GMS fetal group input is needed to decide whether the mode of inheritance for this gene should also include monoallelic cases as the renal phenotype might be detected antenatally e.g. hydronephrosis. The paper describing the CAKUT cases is PMID: 28334964 (Kosfeld et al 2017). |
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| Fetal anomalies v1.847 | PEX6 | Sarah Leigh edited their review of gene: PEX6: Added comment: For Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) has identified Allelic Expression Imbalance (AEI) as a mechanism responsible for the condition. Affected patients (7 unrelated cases) were monoallelic for rs61753230 (c.2578C>T, p.Arg860Trp) and rs144286892 (c.∗442_445 delTAAA), with these variants being on the same chromosome (cis). It would appear that rs144286892 causes the over expression of the allele that it is on, resulting in over expression of rs61753230. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678). Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import (PMID: 29220678).; Changed mode of pathogenicity: Other; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.836 | CHRNE | Arina Puzriakova Tag for-review was removed from gene: CHRNE. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.836 | CHRNB1 | Arina Puzriakova Tag for-review was removed from gene: CHRNB1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.836 | CHRNA3 | Arina Puzriakova Tag for-review was removed from gene: CHRNA3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.836 | CHRNE | Arina Puzriakova commented on gene: CHRNE: The rating of this gene has been updated following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.836 | CHRNB1 | Arina Puzriakova commented on gene: CHRNB1: The rating of this gene has been updated following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.836 | CHRNA3 | Arina Puzriakova commented on gene: CHRNA3: The rating of this gene has been updated following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.835 | CHRNE |
Arina Puzriakova Source Expert Review Green was added to CHRNE. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Fetal anomalies v1.835 | CHRNB1 |
Arina Puzriakova Source Expert Review Green was added to CHRNB1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Fetal anomalies v1.835 | CHRNA3 |
Arina Puzriakova Source Expert Review Green was added to CHRNA3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Fetal anomalies v1.828 | KLF1 | Arina Puzriakova Phenotypes for gene: KLF1 were changed from ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE IV; Hydrops Fetalis to Dyserythropoietic anemia, congenital, type IV, OMIM:613673; Hydrops Fetalis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.826 | MYL9 |
Zornitza Stark changed review comment from: unrelated families Possibly 4th in PMID: 33264186 but specifics including genotype were lacking and overlapping institute/hospital as PMID: 33031641; to: Three unrelated families Possibly 4th in PMID: 33264186 but specifics including genotype were lacking and overlapping institute/hospital as PMID: 33031641 |
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| Fetal anomalies v1.814 | HPRT1 | Arina Puzriakova Phenotypes for gene: HPRT1 were changed from LESCH-NYHAN SYNDROME; GOUT HPRT-RELATED to Hyperuricemia, HRPT-related, OMIM:300323; Lesch-Nyhan syndrome, OMIM:300322 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.813 | KIDINS220 | Arina Puzriakova Phenotypes for gene: KIDINS220 were changed from Spastic paraplegia, intellectual disability, nystagmus, and obesity OMIM:617296; spastic paraplegia, intellectual disability, nystagmus, and obesity MONDO:0015007; cerebral ventriculomegaly; limb contractures to Ventriculomegaly and arthrogryposis, OMIM:619501 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.787 | SLC6A9 | Arina Puzriakova Phenotypes for gene: SLC6A9 were changed from Glycine Encephalopathy with Arthrogryposis to Glycine encephalopathy with normal serum glycine, OMIM:617301; Arthrogryposis, MONDO:0008779 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.768 | FLNC | Arina Puzriakova Phenotypes for gene: FLNC were changed from Arthrogryposis to Arthrogryposis, MONDO:0008779 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.749 | MMP15 |
Dmitrijs Rots gene: MMP15 was added gene: MMP15 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: MMP15 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MMP15 were set to PMID: 33875846 Phenotypes for gene: MMP15 were set to Cholestasis; congenital heart disease Review for gene: MMP15 was set to AMBER Added comment: Three cases from two families with biallelic variants and very similar phenotype including rare combination of symtoms (allagile-like) cholestasis with hepatomegaly and congenital heart disease. Phenotype could be important for fetal panel. Sources: Literature |
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| Fetal anomalies v1.749 | FLNC |
Rhiannon Mellis changed review comment from: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene. Already rated Green on the following other PanelApp panel(s): Distal myopathies Details of review: In this paper by Ravenscroft et al 2020, the proband presented at birth with hip dislocation, clenched hands, adducted thumbs, small mouth and high palate and posteriorly rotated ears. On examination, she had mild arthrogryposis, reduced shoulder movement, elbow dimples and scoliosis. Kiselev et al (PMID: 29858533) also described a series of four cases with early onset restrictive cardiomyopathy (RCM) and congenital myopathy. Two of these also presented with arthrogryposis at birth. Sources: Literature, Expert Review; to: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene. Already rated Green on the following other PanelApp panel(s): Distal myopathies; Neuromuscular disorders; flagged for upgrade to Green on Arthrogryposis panel Details of review: In this paper by Ravenscroft et al 2020, the proband presented at birth with hip dislocation, clenched hands, adducted thumbs, small mouth and high palate and posteriorly rotated ears. On examination, she had mild arthrogryposis, reduced shoulder movement, elbow dimples and scoliosis. Kiselev et al (PMID: 29858533) also described a series of four cases with early onset restrictive cardiomyopathy (RCM) and congenital myopathy. Two of these also presented with arthrogryposis at birth. Sources: Literature, Expert Review |
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| Fetal anomalies v1.749 | FLNC |
Rhiannon Mellis gene: FLNC was added gene: FLNC was added to Fetal anomalies. Sources: Literature,Expert Review Mode of inheritance for gene: FLNC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FLNC were set to PMID: 33060286; 29858533 Phenotypes for gene: FLNC were set to Arthrogryposis Review for gene: FLNC was set to GREEN Added comment: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene. Already rated Green on the following other PanelApp panel(s): Distal myopathies Details of review: In this paper by Ravenscroft et al 2020, the proband presented at birth with hip dislocation, clenched hands, adducted thumbs, small mouth and high palate and posteriorly rotated ears. On examination, she had mild arthrogryposis, reduced shoulder movement, elbow dimples and scoliosis. Kiselev et al (PMID: 29858533) also described a series of four cases with early onset restrictive cardiomyopathy (RCM) and congenital myopathy. Two of these also presented with arthrogryposis at birth. Sources: Literature, Expert Review |
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| Fetal anomalies v1.749 | SLC6A9 | Rhiannon Mellis reviewed gene: SLC6A9: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31875334, 27773429, 32712301, 33269555; Phenotypes: Glycine encephalopathy with Arthrogryposis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.749 | CDK8 |
Rhiannon Mellis gene: CDK8 was added gene: CDK8 was added to Fetal anomalies. Sources: Literature,Expert Review Mode of inheritance for gene: CDK8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CDK8 were set to PMID: 31742715; 30905399 Phenotypes for gene: CDK8 were set to Syndromic developmental disorder with hypotonia and behavioural abnormalities Review for gene: CDK8 was set to GREEN Added comment: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene. Already rated Green on the following other PanelApp panel(s): Intellectual disability; Severe paediatric disorders Details of review: Aggarwal et al 2020 report a heterozygous nonsense variant in a fetus with ventriculomegaly and Ebstein anomaly resulting in IUFD. Post-mortem found additionally congenital diaphragmatic hernia, common atrium and facial dysmorphism. This nonsense variant is at the same position as a hotspot for missense variants reported in a paediatric cohort (Calpena et al 2019, PMID: 30905399) with overlapping but milder phenotype: half of the 12 children in that cohort had cardiac defects, most had dysmorphic features - hence Aggarwal et al propose that this is a more severe (prenatal) presentation of the same multiple malformation syndrome, caused here by a nonsense rather than missense mutation. Sources: Literature, Expert Review |
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| Fetal anomalies v1.731 | ZC4H2 | Ivone Leong Phenotypes for gene: ZC4H2 were changed from ARTHROGRYPOSIS MULTIPLEX CONGENITA AND INTELLECTUAL DISABILITY to Wieacker-Wolff syndrome, OMIM:314580; Wieacker-Wolff syndrome, female-restricted, OMIM:301041 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.726 | BMP2 | Eleanor Williams Added comment: Comment on mode of inheritance: Leaving the mode of inheritance as monoallelic. OMIM also reports the biallelic phenotype of {HFE hemochromatosis, modifier of} but this is not relevant to this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.720 | LONP1 | Zornitza Stark reviewed gene: LONP1: Rating: RED; Mode of pathogenicity: None; Publications: 34547244; Phenotypes: Congenital diaphragmatic hernia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.720 | WNT9B |
Zornitza Stark gene: WNT9B was added gene: WNT9B was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: WNT9B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WNT9B were set to 34145744 Phenotypes for gene: WNT9B were set to Renal agenesis/hypoplasia/dysplasia Review for gene: WNT9B was set to AMBER Added comment: WNT9B plays a key role in the development of the mammalian urogenital system. It is essential for the induction of mesonephric and metanephric tubules, the regulation of renal tubule morphogenesis, and the regulation of renal progenitor cell expansion and differentiation. WNT9B−/− mice have renal agenesis/hypoplasia and reproductive tract abnormalities. Lemire et al. (2021) report 4 individuals from 2 unrelated consanguineous families with bilateral renal agenesis/hypoplasia/dysplasia and homozygous variants in WNT9B. The proband from Family 1 had bilateral renal cystic dysplasia and chronic kidney disease, with 2 deceased siblings with bilateral renal hypoplasia/agenesis. The 3 affected family members were homozygous for a Gly317Arg missense variant in WNT9B. Proband from Family 2 had renal hypoplasia/dysplasia, chronic kidney disease, and was homozygous for a Pro5Alafs*52 nonsense variant in WNT9B. The proband's unaffected brother is also homozygous for the nonsense variant in WNT9B, suggesting nonpenetrance. I wasn't sure which panel this is more pertinent to: we have added this gene to our CAKUT panel. Sources: Literature |
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| Fetal anomalies v1.720 | MED12 |
Eleanor Williams changed review comment from: Comment on mode of inheritance: Variants in this gene have also been reported in females with Hardikar syndrome (Li et al 2021, PMID: 33244166). The phenotype includes facial clefting, pigmentary retinopathy, biliary anomalies, hydronephrosis, and intestinal malrotation. In addition Polla et al 2021 (PMID: 33244165) and Riccardi et al 2021 (PMID: 34079076) report 22 females in total with de novo variants in MED12. Some physical features such as syndactyly (10/22) and anteriorly placed anus (4/22) are noted. 12/22 have severe intellectual disability. X-linked hemizygous mutation in males, monoallelic mutations in females is the appropriate mode of inheritance for Hardikar syndrome but there are carrier implications for the predominantly male-only phenotypes associated with this gene (e.g. Lujan-Fryns syndrome, Ohdo syndrome, X-linked and Opitz-Kaveggia syndrome) in female cases. ; to: Comment on mode of inheritance: Variants in this gene have also been reported in females with Hardikar syndrome (Li et al 2021, PMID: 33244166). The phenotype includes facial clefting, pigmentary retinopathy, biliary anomalies, hydronephrosis, and intestinal malrotation. In addition Polla et al 2021 (PMID: 33244165) and Riccardi et al 2021 (PMID: 34079076) report 22 females in total with de novo variants in MED12. Some physical features such as syndactyly (10/22) and anteriorly placed anus (4/22) are noted. 12/22 have severe intellectual disability. X-linked hemizygous mutation in males, monoallelic mutations in females is the appropriate mode of inheritance for Hardikar syndrome but there are carrier implications for the predominantly male-only phenotypes associated with this gene (e.g. Lujan-Fryns syndrome, Ohdo syndrome, X-linked and Opitz-Kaveggia syndrome) in female cases, therefore waiting for GMS review before considering changing the mode of inheritance. |
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| Fetal anomalies v1.720 | MED12 |
Eleanor Williams changed review comment from: Comment on mode of inheritance: Variants in this gene have also been reported in females with Hardikar syndrome (the phenotype that includes facial clefting, pigmentary retinopathy, biliary anomalies, hydronephrosis, and intestinal malrotation). In addition Polla et al 2021 (PMID: 33244165) and Riccardi et al 2021 (PMID: 34079076) report 22 females in total with de novo variants in MED12. Some physical features such as syndactyly (10/22) and anteriorly placed anus (4/22) also noted. 12/22 have severe intellectual disability. X-linked hemizygous mutation in males, monoallelic mutations in females is the appropriate mode of inheritance for Hardikar syndrome but there are carrier implications for the predominantly male-only phenotypes associated with this gene (e.g. Lujan-Fryns syndrome, Ohdo syndrome, X-linked and Opitz-Kaveggia syndrome) in female cases. ; to: Comment on mode of inheritance: Variants in this gene have also been reported in females with Hardikar syndrome (Li et al 2021, PMID: 33244166). The phenotype includes facial clefting, pigmentary retinopathy, biliary anomalies, hydronephrosis, and intestinal malrotation. In addition Polla et al 2021 (PMID: 33244165) and Riccardi et al 2021 (PMID: 34079076) report 22 females in total with de novo variants in MED12. Some physical features such as syndactyly (10/22) and anteriorly placed anus (4/22) are noted. 12/22 have severe intellectual disability. X-linked hemizygous mutation in males, monoallelic mutations in females is the appropriate mode of inheritance for Hardikar syndrome but there are carrier implications for the predominantly male-only phenotypes associated with this gene (e.g. Lujan-Fryns syndrome, Ohdo syndrome, X-linked and Opitz-Kaveggia syndrome) in female cases. |
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| Fetal anomalies v1.720 | MED12 |
Eleanor Williams changed review comment from: Comment on mode of inheritance: Variants in this gene have also been reported in females with Hardikar syndrome and phenotype that includes facial clefting, pigmentary retinopathy, biliary anomalies, hydronephrosis, and intestinal malrotation. X-linked hemizygous mutation in males, monoallelic mutations in females is the appropriate mode of inheritance for Hardikar syndrome but there are carrier implications for the male-only phenotypes associated with this gene (e.g. Lujan-Fryns syndrome, Ohdo syndrome, X-linked and Opitz-Kaveggia syndrome) in female cases; to: Comment on mode of inheritance: Variants in this gene have also been reported in females with Hardikar syndrome (the phenotype that includes facial clefting, pigmentary retinopathy, biliary anomalies, hydronephrosis, and intestinal malrotation). In addition Polla et al 2021 (PMID: 33244165) and Riccardi et al 2021 (PMID: 34079076) report 22 females in total with de novo variants in MED12. Some physical features such as syndactyly (10/22) and anteriorly placed anus (4/22) also noted. 12/22 have severe intellectual disability. X-linked hemizygous mutation in males, monoallelic mutations in females is the appropriate mode of inheritance for Hardikar syndrome but there are carrier implications for the predominantly male-only phenotypes associated with this gene (e.g. Lujan-Fryns syndrome, Ohdo syndrome, X-linked and Opitz-Kaveggia syndrome) in female cases. |
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| Fetal anomalies v1.718 | MED12 |
Eleanor Williams Added comment: Comment on mode of inheritance: Variants in this gene have also been reported in females with Hardikar syndrome and phenotype that includes facial clefting, pigmentary retinopathy, biliary anomalies, hydronephrosis, and intestinal malrotation. X-linked hemizygous mutation in males, monoallelic mutations in females is the appropriate mode of inheritance for Hardikar syndrome but there are carrier implications for the male-only phenotypes associated with this gene (e.g. Lujan-Fryns syndrome, Ohdo syndrome, X-linked and Opitz-Kaveggia syndrome) in female cases |
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| Fetal anomalies v1.713 | CNTN1 | Arina Puzriakova Entity copied from Arthrogryposis v3.122 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.692 | MYOD1 |
Ivone Leong gene: MYOD1 was added gene: MYOD1 was added to Fetal anomalies. Sources: Expert Review Amber,Literature Q3_21_rating tags were added to gene: MYOD1. Mode of inheritance for gene: MYOD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MYOD1 were set to 26733463; 30403323; 31260566 Phenotypes for gene: MYOD1 were set to Myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies, OMIM:618975 |
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| Fetal anomalies v1.645 | FOXP4 |
Ivone Leong gene: FOXP4 was added gene: FOXP4 was added to Fetal anomalies. Sources: Literature Q2_21_rating, Q2_21_phenotype tags were added to gene: FOXP4. Mode of inheritance for gene: FOXP4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: FOXP4 were set to 33110267 Phenotypes for gene: FOXP4 were set to Neurodevelopmental disorder; multiple congenital abnormalities Review for gene: FOXP4 was set to AMBER Added comment: This gene is associated with a phenotype in Gene2Phenotype but not in OMIM. This gene is present as an Amber gene on the Intellectual disability panel (Version 3.1052) with the following reviews: "This gene is a little bit difficult to place, may be Green on Fetal Anomalies panel? Eight unrelated individuals reported, seven de novo missense, and one individual with a truncating variant. Detailed phenotypic information available on 6. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia (2/6), cervical spine abnormalities, and ptosis. Intellectual disability described as mild in 2, some had normal intellect despite the early speech and language delays, hence Amber rating here. Sources: Literature Zornitza Stark (Australian Genomics), 4 Nov 2020" "Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). As ID is not present in the majority of affected patients, and the affected individuals only show mild ID, this gene has been given an Amber rating. Ivone Leong (Genomics England Curator), 4 Dec 2020" After discussion with the Genomics England Clinical Team it was decided that this gene should be added to this panel as an Amber gene and subject to review by the GMS specialist group. Sources: Literature |
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| Fetal anomalies v1.630 | CDAN1 | Arina Puzriakova Phenotypes for gene: CDAN1 were changed from Anemia, congenital dyserythropoietic, type I 224120 to Dyserythropoietic anemia, congenital, type Ia, OMIM:224120; Anemia, congenital dyserythropoietic, type 1a, MONDO:0009135 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.628 | CDAN1 | Arina Puzriakova reviewed gene: CDAN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30786798, 29668551, 29599085; Phenotypes: Dyserythropoietic anemia, congenital, type Ia, OMIM:224120, Anemia, congenital dyserythropoietic, type 1a, MONDO:0009135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.627 | WBP11 |
Eleanor Williams gene: WBP11 was added gene: WBP11 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: WBP11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: WBP11 were set to 33276377 Phenotypes for gene: WBP11 were set to malformation syndrome affecting the cardiac, skeletal, gastrointestinal and renal systems Review for gene: WBP11 was set to GREEN Added comment: PMID: 33276377 - Martin et al 2020 - report 13 affected individuals from 7 unrelated families identified through various different cohort analysis (vertebral malformation, renal hypodysplasia, syndromic esophageal atresia, multiple congenital anomalies) in whom a WBP11 heterozygous variant is considered the top causative candidate. 5 identified variants were predicted to be protein truncating whilst the 6th was a missense variant. All variants are absent from population databases. In family 1, the variant was inherited from the apparently unaffected mother, indicating reduced penetrance, and phenotypic variance within families was observed. Phenotypes covered cardiac, vertebral, renal, craniofacial and gastrointestinal systems. At least at least 5 of the patients affected had features in three component organs so can be considered a VACTERL association. Wbp11 heterozygous null mice had vertebral and renal anomalies. Sources: Literature |
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| Fetal anomalies v1.625 | OTUD5 |
Arina Puzriakova gene: OTUD5 was added gene: OTUD5 was added to Fetal anomalies. Sources: Expert Review Q2_21_rating tags were added to gene: OTUD5. Mode of inheritance for gene: OTUD5 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: OTUD5 were set to 33131077; 33523931 Phenotypes for gene: OTUD5 were set to Multiple congenital anomalies-neurodevelopmental syndrome, X-linked, OMIM:301056 Review for gene: OTUD5 was set to GREEN Added comment: OTUD5 is associated with a relevant phenotype in OMIM but not yet in Gene2Phenotype. - PMID: 33131077 (2021) - 13 male patients from a single family with three generations affected. Patients presented prenatally or during the neonatal period with IUGR, ventriculomegaly, hydrocephalus, hypotonia, congenital heart defects, hypospadias, and severe neurodevelopmental delay. The disease is typically fatal during infancy, mainly due to sepsis (pneumonias). Female carriers are asymptomatic. WGS in four individuals identified a unique candidate variant in the OTUD5 gene (NM_017602.3:c.598G > A, p.Glu200Lys). The variant cosegregated with the disease in 10 tested individuals. - PMID: 33523931 (2021) - Another 10 individuals from 7 families reported. Key features include poor growth, global developmental delay with impaired intellectual development, and variable abnormalities of the cardiac, skeletal, and genitourinary systems. Most affected individuals also have hypotonia and dysmorphic craniofacial features. Brain imaging typically shows enlarged ventricles and thin corpus callosum; some have microcephaly, whereas others have hydrocephalus. The severity of the disorder is highly variable, ranging from death in early infancy to survival into the second or third decade. Sources: Expert Review |
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| Fetal anomalies v1.624 | SYNE1 | Arina Puzriakova Phenotypes for gene: SYNE1 were changed from SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 8; EMERY-DREIFUSS MUSCULAR DYSTROPHY 4, AUTOSOMAL RECESSIVE to Arthrogryposis multiplex congenita 3, myogenic type, OMIM:618484; Arthrogryposis multiplex congenita 3, myogenic type, MONDO:0032778 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.622 | SYNE1 | Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber but there is sufficient evidence to promote to Green at the next GMS panel update - at least 3 unrelated cases with arthrogryposis multiplex congenita (AMC) which may be detected prenatally. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.621 | SYNE1 | Arina Puzriakova reviewed gene: SYNE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19542096, 24319099, 27782104; Phenotypes: Arthrogryposis multiplex congenita 3, myogenic type, OMIM:618484, Arthrogryposis multiplex congenita 3, myogenic type, MONDO:0032778; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.617 | SLC20A1 |
Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Rating Amber but there is sufficient evidence to promote to Green. At least three unrelated families with a BEEC phenotype (fetally-relevant) and different heterozygous variants in this gene (PMID: 32850778). In vitro assays and zebrafish model support pathogenicity. |
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| Fetal anomalies v1.612 | SUFU |
Arina Puzriakova changed review comment from: The patients described by Schroder et al 2020 (PMID: 33024317) display cerebellar abnormalities that were said to be within the milder range of the Joubert clinical spectrum. This gene will be flagged for review by the GMS team with regards to whether these features may conceivably be detected prenatally (added 'for-review' tag). Note that these individuals harboured heterozygous truncating variants, and monoallelic variants in this gene have also previously been associated with Basal cell nevus syndrome and Medulloblastoma.; to: SUFU was reassessed in line with the recent expert review by Rhiannon Mellis (GOSH). The patients described by Schroder et al 2020 (PMID: 33024317) display cerebellar abnormalities that were said to be within the milder range of the Joubert clinical spectrum. However, it is unclear whether these features may conceivably be detected prenatally and therefore this gene will be flagged for review by the GMS team with regards to phenotypic fit for this panel (added 'for-review' tag). Note that unlike the 2 Joubert syndrome families with biallelic variants reported by De Mori et al. (2017, PMID: 28965847), these individuals harboured heterozygous truncating variants in the SUFU gene. Monoallelic variants have previously been associated with basal cell nevus syndrome and medulloblastoma, and there was no evidence of tumours in any of the families described by Schroder et al. |
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| Fetal anomalies v1.609 | SMPD4 | Arina Puzriakova Phenotypes for gene: SMPD4 were changed from Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies to Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies, OMIM:618622; Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies, MONDO:0032838 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.483 | OSGEP | Arina Puzriakova Phenotypes for gene: OSGEP were changed from Nephrotic syndrome with primary microcephaly to Galloway-Mowat syndrome 3, OMIM:617729; Galloway-Mowat syndrome 3, MONDO:0033007 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.480 | NEK8 | Arina Puzriakova Phenotypes for gene: NEK8 were changed from RENAL-HEPATIC-PANCREATIC DYSPLASIA 2; NEPHRONOPHTHISIS 9 to ?Nephronophthisis 9, OMIM:613824; Nephronophthisis 9, MONDO:0013444; Renal-hepatic-pancreatic dysplasia 2, OMIM:615415; Renal-hepatic-pancreatic dysplasia 2, MONDO:0014174 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.336 | CCDC8 | Arina Puzriakova Phenotypes for gene: CCDC8 were changed from THREE M SYNDROME 3 to 3-M syndrome 3, OMIM:614205; 3M syndrome 3, MONDO:0013627 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.312 | CHRNE | Arina Puzriakova Classified gene: CHRNE as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.312 | CHRNE | Arina Puzriakova Gene: chrne has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.311 | CHRNE | Arina Puzriakova Tag for-review tag was added to gene: CHRNE. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.311 | CHRNB1 | Arina Puzriakova Classified gene: CHRNB1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.311 | CHRNB1 | Arina Puzriakova Gene: chrnb1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.310 | CHRNB1 | Arina Puzriakova Tag for-review tag was added to gene: CHRNB1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.310 | CHRNA3 | Arina Puzriakova Classified gene: CHRNA3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.310 | CHRNA3 | Arina Puzriakova Gene: chrna3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.309 | CHRNA3 | Arina Puzriakova Tag for-review tag was added to gene: CHRNA3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.229 | AMMECR1 |
Rhiannon Mellis gene: AMMECR1 was added gene: AMMECR1 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: AMMECR1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: AMMECR1 were set to Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis, 300990 Review for gene: AMMECR1 was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Green on related panel(s): IUGR and IGF abnormalities Sources: Expert list |
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| Fetal anomalies v1.229 | ANKS6 |
Rhiannon Mellis gene: ANKS6 was added gene: ANKS6 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: ANKS6 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ANKS6 were set to Nephronophthisis 16, 615382 Review for gene: ANKS6 was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Green on related panel(s): Cystic renal disease (super panel); Rare multisystem ciliopathy Super panel Sources: Expert list |
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| Fetal anomalies v1.229 | B4GAT1 |
Rhiannon Mellis gene: B4GAT1 was added gene: B4GAT1 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: B4GAT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: B4GAT1 were set to PMID: 23877401; 23359570 Phenotypes for gene: B4GAT1 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13, 615287 Review for gene: B4GAT1 was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Green on related panel(s): Arthrogryposis; Neuromuscular disorders Additional comment: Severe structural brain phenotype and dysplastic kidneys, reported onset in utero. PMID: 23877401; PMID: 23359570 Sources: Expert list |
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| Fetal anomalies v1.229 | CHRNA3 |
Rhiannon Mellis gene: CHRNA3 was added gene: CHRNA3 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: CHRNA3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CHRNA3 were set to Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary CAKUT, 191800 Review for gene: CHRNA3 was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Green on related panel(s): CAKUT Sources: Expert list |
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| Fetal anomalies v1.229 | CHRNB1 |
Rhiannon Mellis gene: CHRNB1 was added gene: CHRNB1 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: CHRNB1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: CHRNB1 were set to Myasthenic syndrome, congenital, 2A, slow-channel, 616313; ?Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency, 616314 Review for gene: CHRNB1 was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Green on related panel(s): Arthrogryposis; Neuromuscular disorders Sources: Expert list |
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| Fetal anomalies v1.229 | CHRNE |
Rhiannon Mellis gene: CHRNE was added gene: CHRNE was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: CHRNE was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: CHRNE were set to Myasthenic syndrome, congenital, 4A, slow-channel, 605809; Myasthenic syndrome, congenital, 4B, fast-channel, 616324; Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency, 608931 Review for gene: CHRNE was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Green on related panel(s): Arthrogryposis; Neuromuscular disorders Additional comment: Phenotype on OMIM reported as including arthrogryposis multiplex in severe cases. Decreased fetal movements in some cases. Sources: Expert list |
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| Fetal anomalies v1.228 | COL12A1 |
Rhiannon Mellis gene: COL12A1 was added gene: COL12A1 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: COL12A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: COL12A1 were set to Bethlem myopathy 2, 616471; ?Ullrich congenital muscular dystrophy 2, 616470 Review for gene: COL12A1 was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Green on related panel(s): Arthrogryposis Additional comment: At least three affected families with Bethlem myopathy which is associated with early contractures (?congenital) as well as two brothers with Ulrich congenital muscular dystrophy which is associated with arthrogryposis Sources: Expert list |
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| Fetal anomalies v1.228 | COLQ |
Rhiannon Mellis gene: COLQ was added gene: COLQ was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: COLQ was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COLQ were set to PMID: 9689136; 11865139 Phenotypes for gene: COLQ were set to Myasthenic syndrome, congenital, 5, 603034 Review for gene: COLQ was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Green on related panel(s): Arthrogryposis Additional comment: I can’t see any reported cases specifically with arthrogryposis, but some cases presented at birth with hypotonia/weakness/fatigability. PMID: 9689136; 11865139. Therefore included on basis of severe neonatal phenotype that may conceivably also present prenatally. Sources: Expert list |
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| Fetal anomalies v1.215 | DNM2 |
Rhiannon Mellis gene: DNM2 was added gene: DNM2 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: DNM2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: DNM2 were set to PMID: 30208955 Phenotypes for gene: DNM2 were set to Lethal congenital contracture syndrome 5, 615368 Review for gene: DNM2 was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Green on related panel(s): Arthrogryposis Additional comment: AR Phenotype = lethal congenital contracture syndrome – definite prenatal phenotype with arthrogryposis, decreased fetal movements, polyhydramnios. Mutations only identified in three siblings although supported by animal models --> Moderate evidence for arthrogryposis --> Made green on arthrogryposis panel after internal discussion (Jan 2017) NB in 2018 a further report of 3 unrelated cases with heterozygous DNM2 pathogenic variants with a more severe phenotype than usual for the AD disease (centronuclear myopathy) – all 3 had severe hypotonia and respiratory distress from birth. 1 had reduced fetal movements, polyhydramnios, distal contractures at birth (born at 29/40). 1 had micrognathia and clenched fists prenatally, multiple contractures at birth. All 3 were ventilator-dependent and died within first few months of life. (i.e. some overlap with the lethal congenital contracture phenotype despite heterozygous variants). PMID: 30208955 Sources: Expert list |
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| Fetal anomalies v1.215 | FKBP10 |
Rhiannon Mellis gene: FKBP10 was added gene: FKBP10 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: FKBP10 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FKBP10 were set to Bruck syndrome 1; Osteogenesis imperfecta, type XI Review for gene: FKBP10 was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Green on related panel(s): Arthrogryposis; Osteogenesis imperfecta; Skeletal dysplasia Sources: Expert list |
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| Fetal anomalies v1.214 | MYH2 |
Rhiannon Mellis gene: MYH2 was added gene: MYH2 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: MYH2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: MYH2 were set to Proximal myopathy and ophthalmoplegia Review for gene: MYH2 was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Green on related panel(s): Arthrogryposis; Neuromuscular disorders Additional comments: Congenital contractures in some which improve with time - Contractures at birth are described (in some cases) so could be detected prenatally. Sources: Expert list |
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| Fetal anomalies v1.214 | MYH7 |
Rhiannon Mellis gene: MYH7 was added gene: MYH7 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: MYH7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: MYH7 were set to PMID: 22859017; 25547560; 26337809 Phenotypes for gene: MYH7 were set to Cardiomyopathy, dilated, 1S; Cardiomyopathy, hypertrophic, 1; Laing distal myopathy; Left ventricular noncompaction 5 Review for gene: MYH7 was set to GREEN Added comment: Currently Green on arthrogryposis panel but no clear association with arthrogryposis in literature, it seems to be a more a slowly progressive myopathy phenotype. However, there are four reported cases of fetal cardiomyopathy related to MYH7, detectable on ultrasound. PMID: 22859017, PMID: 25547560, PMID: 26337809 Sources: Literature |
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| Fetal anomalies v1.214 | MYL1 |
Rhiannon Mellis gene: MYL1 was added gene: MYL1 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: MYL1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MYL1 were set to PMID: 30215711 Phenotypes for gene: MYL1 were set to Myopathy, congenital, with fast-twitch (type II) fiber atrophy Review for gene: MYL1 was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Green on related panel(s): Arthrogryposis; Neuromuscular disorders Additional comment: Predominant phenotype is severe hypotonia and respiratory failure from birth. 2 patients are reported: one had polyhydramnios and normal fetal movements, with mild flexion contractures at birth. The other had normal liquor volume, reduced fetal movements, no contractures. (PMID: 30215711). But severe neonatal phenotype so include as relevant. Sources: Expert list |
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| Fetal anomalies v1.214 | MYMK |
Rhiannon Mellis gene: MYMK was added gene: MYMK was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: MYMK was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: MYMK were set to Carey-Fineman-Ziter syndrome Review for gene: MYMK was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Green on related panel(s): Arthrogryposis; Clefting; Hydrocephalus; Neuromuscular disorders Additional comment: Phenotype includes congenital contractures, talipes, Pierre-Robin sequence, clefts, reduced fetal movements. Sources: Expert list |
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| Fetal anomalies v1.214 | NEK8 | Rhiannon Mellis reviewed gene: NEK8: Rating: GREEN; Mode of pathogenicity: None; Publications: 18199800, 23418306, 26967905, 26697755, 26862157; Phenotypes: NEPHRONOPHTHISIS 9, RENAL-HEPATIC-PANCREATIC DYSPLASIA 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.214 | TOR1A | Arina Puzriakova Phenotypes for gene: TOR1A were changed from Arthrogryposis multiplex congenita 5 to Arthrogryposis multiplex congenita 5, OMIM:618947; Arthrogryposis multiplex congenita 5, MONDO:0100218 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.211 | TNNT3 | Arina Puzriakova Phenotypes for gene: TNNT3 were changed from Arthrogryposis, distal, type 2B2 to Arthrogryposis, distal, type 2B2, OMIM:618435; Arthrogryposis, distal, type 2B2, MONDO:0032750 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.209 | PFKM |
Rhiannon Mellis gene: PFKM was added gene: PFKM was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: PFKM was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PFKM were set to Glycogen storage disease VII Review for gene: PFKM was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Green on related panel(s): Arthrogryposis; Neuromuscular disorders Additional comment: literature supports arthrogryposis in severe infantile form Sources: Expert list, Literature |
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| Fetal anomalies v1.195 | SCLT1 |
Rhiannon Mellis gene: SCLT1 was added gene: SCLT1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: SCLT1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SCLT1 were set to No OMIM phenotype; Oro-facio-digital syndrome type IX; Senior-Løken Syndrome Review for gene: SCLT1 was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Green on related panel(s): Rare multisystem ciliopathy Super panel Copied from rare multisystem ciliopathies panel: PMID: 24285566 - Adly et al 2014 - 1 case with index patient with consanguineous Saudi parents and a severe ciliopathy phenotype. He had severe midline cleft lip and palate, microcephaly and choanal atresia. He also had significant eye involvement in the form of severe coloboma, and congenital heart disease (ASD and VSD). He had micropenis. Brain imaging revealed pachygyria and absent corpus callosum. He had abnormal inner ear structures. A splicing mutation was identified in SCLT1 (, NM_144643.2:exon5:c.290+2T>C). This mutation completely abolishes the consensus donor site of exon 5 as confirmed by RTPCR, which showed complete skipping of exon 5 resulting in a frameshift and introduction of a premature stop codon (p.Lys79Valfs*4), PMID: 28005958 - de Castro-Miró et al 2016 - A cohort of 33 pedigrees affected with a variety of retinal disorders was analysed by WES. 1 case with compound heterozygosity (one missense and one splicing altering mutations) in SCLT1 that segregates with the condition in the family (2 affected siblings). Proposed to be causative of early-onset Retinitis Pigmentosa. SCLT1 is a member of the centrosomal/ciliary protein family. PMID: 28486600 - Li et al 2017 - report a mouse model with mutated Sclt1 gene. The Sclt1-/- mice exhibit typical ciliopathy phenotypes, including cystic kidney, cleft palate and polydactyly. PMID: 30425282 - Katagiri et al 2018 - a patient with Senior Løken syndrome and her unaffected parents revealed that the patient had infantile-onset retinal dystrophy and juvenile-onset nephronophthisis. Other systemic abnormalities included hepatic dysfunction, megacystis, mild learning disability, autism, obesity, and hyperinsulinemia. Whole-exome sequencing identified compound heterozygous SCLT1 variants (c.1218 + 3insT and c.1631A > G) in the patient. The unaffected parents were heterozygous for each variant. Transcript analysis using reverse transcription PCR demonstrated that the c.1218 + 3insT variant leads to exon 14 skipping (p.V383_M406del), while the other variant (c.1631A > G) primarily leads to exon 17 skipping (p.D480EfsX11) as well as minor amounts of two transcripts. Immunohistochemical analysis demonstrated that the Sclt1 protein was localized to the distal appendage of the photoreceptor basal body, indicating a ciliary protein. = 3 cases plus a mouse model and functional evidence that the protein is a ciliary protein. Sources: Literature |
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| Fetal anomalies v1.187 | SMPD4 |
Rhiannon Mellis gene: SMPD4 was added gene: SMPD4 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: SMPD4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SMPD4 were set to PMID: 31495489 Phenotypes for gene: SMPD4 were set to Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies Review for gene: SMPD4 was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Green on related panel(s): Arthrogryposis; Cerebellar hypoplasia Additional comment: Documented fetal phenotype with IUGR, microcephaly, arthrogryposis, and structural brain anomalies in some. (32 reported cases from 12 families) PMID: 31495489 Sources: Literature |
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| Fetal anomalies v1.187 | STAC3 |
Rhiannon Mellis gene: STAC3 was added gene: STAC3 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: STAC3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: STAC3 were set to PMID: 30168660 Phenotypes for gene: STAC3 were set to Myopathy, congenital, Baily-Bloch Review for gene: STAC3 was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Additional comment: Documented arthrogryposis, also cleft palate, polyhydramnios and reduced fetal movements. PMID: 30168660 Sources: Literature |
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| Fetal anomalies v1.185 | TNNT3 |
Rhiannon Mellis gene: TNNT3 was added gene: TNNT3 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: TNNT3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TNNT3 were set to 32779773 Phenotypes for gene: TNNT3 were set to Arthrogryposis, distal, type 2B2 Mode of pathogenicity for gene: TNNT3 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: TNNT3 was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Additional comment: Clearly documented phenotype of distal arthrogryposis. Also, recent paper in Prenatal Diagnosis reporting a het pathogenic variant in TNNT3 in a fetus with FADS; that variant has previously only been described in a family with much milder distal arthrogryposis phenotype. PMID: 32779773 (copied from OMIM): In in vitro studies, Robinson et al. (2007) demonstrated that the TNNI2 R174Q (191043.0001) and R156X (191043.0002) mutations and the TNNT3 mutation R63H (600692.0001) resulted in a gain of function with increased ATPase activity in actin-activated myosin ATPase assays, reflecting increased calcium sensitivity and consistent with increased contractility. In patients, Robinson et al. (2007) concluded that the mutation would cause increased tension in developing muscles, thus resulting in contractures and limb deformities via an active process rather than a passive process. These findings implicated disturbed muscle function as the pathogenic mechanism underlying DA2B. Sources: Literature |
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| Fetal anomalies v1.185 | TOR1A |
Rhiannon Mellis gene: TOR1A was added gene: TOR1A was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: TOR1A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TOR1A were set to 30244176; 29053766; 28516161 Phenotypes for gene: TOR1A were set to Arthrogryposis multiplex congenita 5 Review for gene: TOR1A was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Additional comment: documented phenotype of severe arthrogryposis multiplex congenital with prenatal onset Sources: Literature |
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| Fetal anomalies v1.185 | TXNDC15 |
Rhiannon Mellis gene: TXNDC15 was added gene: TXNDC15 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: TXNDC15 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TXNDC15 were set to Meckel Gruber syndrome Review for gene: TXNDC15 was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel (Cystic renal disease (super panel); Limb disorders; Rare multisystem ciliopathy Super panel). Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Comment from copied from skeletal ciliopathies panel: Shaheen et al. 2016 (PMID:27894351) report TXNDC15 variants in two consanguineous Saudi families that share the features of Meckel-Gruber syndrome (a ciliopathy phenotype). Phenotypes of both patients included polydactyly; one patients was still born, and one survived till 11 hours old. Furthermore, through an international collaboration, they were able to identify an additional Meckel-Gruber syndrome patient (Pakistani origin) with a homozygous truncating variant in this gene. The patient also had polydactyly, although a sibling presented similarly but with no polydactyl. Patient fibroblasts had aberrant ciliogenesis. Sources: Other Sources: Literature |
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| Fetal anomalies v1.184 | NUAK2 |
Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Single consanguineous family with three consecutive fetuses with anencephaly. Exome sequencing revealed a recessive 21-bp in-frame deletion in NUAK2 segregating with the disease. Pathogenicity is supported by in vitro and animal model data. Rating Amber, awaiting further cases/clinical evidence prior to inclusion as diagnostic-grade (added 'watchlist' tag) |
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| Fetal anomalies v1.179 | SHROOM4 | Arina Puzriakova Classified gene: SHROOM4 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.179 | SHROOM4 | Arina Puzriakova Gene: shroom4 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.178 | SHROOM4 | Arina Puzriakova Phenotypes for gene: SHROOM4 were changed from HP:0001274 to Stocco dos Santos X-linked mental retardation syndrome, 300434 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.156 | NEK9 | Arina Puzriakova Phenotypes for gene: NEK9 were changed from Lethal congenital contracture syndrome 10 617022 to ?Arthrogryposis, Perthes disease, and upward gaze palsy, OMIM:614262; Arthrogryposis, Perthes disease, and upward gaze palsy, MONDO:0013660; Lethal congenital contracture syndrome 10, OMIM:617022; NEK9-related lethal skeletal dysplasia, MONDO:0014870 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.155 | MN1 |
Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Multiple unrelated individuals (>20) described with a complex developmental disorder and de novo truncating MN1 variants. This gene will be flagged for review to determine whether the phenotype is fetally-relevant and there is enough evidence to include as Green. Plausible that some features of the disorder, such as craniofacial abnormalities and structural brain anomalies may be detected prenatally. However based on published clinical descriptions, antenatal history was uneventful in most cases - but reports did include fetal brain anomalies (1), NICU admission (1) and IUGR (2). Similarly, neonatal problems were only reported in a few patients but included respiratory issues (3), abnormal ABR (1), congenital diaphragmatic hernia (1), perinatal hypoxia (1), congenital hypothyroidism (1), hearing impairment (1) and SCBU admission (1) (see Supplementary material in PMID: 31834374) |
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| Fetal anomalies v1.147 | TMEM107 |
Arina Puzriakova changed review comment from: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Associated with relevant phenotype in OMIM, but not in Gen2Phen at present. Biallelic variants identified in at least 5 unrelated families with a range of ciliopathic defects including oral-facial-digital syndrome (PMID: 26518474), Meckel-Gruber syndrome (PMID: 26123494), and Joubert syndrome (PMID: 26595381). Phenotype is fetally-relevant in the two apparently unrelated MKS-13 infants, although it should be noted that they were found to share a single haplotype (founder effect). However, it is unclear whether this panel is relevant to OFD case, which would be necessary to reach the threshold for inclusion of TMEM107 as Green. Therefore, rating Amber but will be flagged at the next GMS panel review to assess the phenotypic relevance in context of the panel scope (added 'for-review' tag); to: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Associated with relevant phenotype in OMIM, but not in Gen2Phen at present. Biallelic variants identified in at least 5 unrelated families with a range of ciliopathic defects including oral-facial-digital syndrome (PMID: 26518474 and 26595381), Meckel-Gruber syndrome (PMID: 26123494), and Joubert syndrome (PMID: 26595381). Phenotype is fetally-relevant in the two unrelated MKS-13 infants, although it should be noted that they were found to share a single haplotype (founder effect), as well as the OFD syndrome cases. Rating Amber but should be promoted to Green at the next GMS panel update (added 'for-review' tag) |
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| Fetal anomalies v1.147 | TMEM107 |
Arina Puzriakova changed review comment from: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Associated with relevant phenotype in OMIM, but not in Gen2Phen at present. Biallelic variants identified in at least 5 unrelated families with a range of ciliopathic defects including oral-facial-digital syndrome (PMID: 26518474), Meckel-Gruber syndrome (PMID: 26123494), and Joubert syndrome (PMID: 26595381). Phenotype is fetally-relevant in the two apparently unrelated MKS-13 infants, although it should be noted that they were found to share a single haplotype (founder effect). However, it is unclear whether this panel would be applicable in OFD case which would be necessary to reach the threshold for inclusion of TMEM107 as Green. Therefore, rating Amber but will be flagged at the next GMS panel review to assess the phenotypic relevance in context of the panel scope (added 'for-review' tag); to: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Associated with relevant phenotype in OMIM, but not in Gen2Phen at present. Biallelic variants identified in at least 5 unrelated families with a range of ciliopathic defects including oral-facial-digital syndrome (PMID: 26518474), Meckel-Gruber syndrome (PMID: 26123494), and Joubert syndrome (PMID: 26595381). Phenotype is fetally-relevant in the two apparently unrelated MKS-13 infants, although it should be noted that they were found to share a single haplotype (founder effect). However, it is unclear whether this panel is relevant to OFD case, which would be necessary to reach the threshold for inclusion of TMEM107 as Green. Therefore, rating Amber but will be flagged at the next GMS panel review to assess the phenotypic relevance in context of the panel scope (added 'for-review' tag) |
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| Fetal anomalies v1.147 | TMEM107 |
Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Associated with relevant phenotype in OMIM, but not in Gen2Phen at present. Biallelic variants identified in at least 5 unrelated families with a range of ciliopathic defects including oral-facial-digital syndrome (PMID: 26518474), Meckel-Gruber syndrome (PMID: 26123494), and Joubert syndrome (PMID: 26595381). Phenotype is fetally-relevant in the two apparently unrelated MKS-13 infants, although it should be noted that they were found to share a single haplotype (founder effect). However, it is unclear whether this panel would be applicable in OFD case which would be necessary to reach the threshold for inclusion of TMEM107 as Green. Therefore, rating Amber but will be flagged at the next GMS panel review to assess the phenotypic relevance in context of the panel scope (added 'for-review' tag) |
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| Fetal anomalies v1.118 | SCN1A | Arina Puzriakova Phenotypes for gene: SCN1A were changed from SCN1A-RELATED SEIZURE DISORDERS to Dravet syndrome, OMIM:607208; Arthrogryposis multiplex congenita | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.116 | SCN1A | Arina Puzriakova Added comment: Comment on list classification: Although it is anticipated that following birth early-onset seizures will likely represent the predominant characteristic of the phenotype, arthrogryposis multiplex congenita may be detected in utero as demonstrated with the cases in PMID:32928894. Therefore, this gene will be flagged for review at the next GMS panel update to assess whether this is sufficient for inclusion on this panel (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.115 | SCN1A | Arina Puzriakova reviewed gene: SCN1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 32928894, 29543227; Phenotypes: Dravet syndrome, OMIM:607208, Arthrogryposis multiplex congenita; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.107 | NEK9 |
Rhiannon Mellis edited their review of gene: NEK9: Added comment: Deden et al (2020) report a further family with two consecutive prenatal presentations with compound heterozygous NEK9 variants. Both fetuses had arthrogryposis. Both variants were reported as VUS when detected in the first fetus, which initially presented with 'short long bones, bowed femur, micrognathia, talipes and deviated hand' but re-evaluated after the phenotype progressed to arthrogryposis and then the next pregnancy showed the same ultrasound abnormalities and the same compound het variants. At this point the authors felt this represented a conclusive diagnosis.; Changed rating: GREEN; Changed publications: PMID: 26908619, 26633546, 32333414; Changed phenotypes: Arthrogryposis, short long bones |
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| Fetal anomalies v1.104 | USP18 |
Arina Puzriakova Added comment: Comment on list classification: With addition of the recently reported case (PMID:31940699) there is now a total of three families with pseudo-TORCH syndrome due to biallelic variants in USP18 (two carrying the same founder variant). A rating upgrade from Amber to Green should be considered and therefore this gene will be flagged for review at the date of next GMS panel update (added 'for-review' tag). |
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| Fetal anomalies v1.97 | NUAK2 |
Zornitza Stark gene: NUAK2 was added gene: NUAK2 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: NUAK2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUAK2 were set to 32845958 Phenotypes for gene: NUAK2 were set to Anencephaly Review for gene: NUAK2 was set to AMBER Added comment: Novel gene described in single consanguineous family with three FDIU and extensive anencephaly. Hom inframe del affecting functional kinase domain, parents confirmed carriers. Good functional data showing loss of enzyme function and mouse model with 40% anencephaly after knock-out. Sources: Literature |
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| Fetal anomalies v1.95 | SLC20A1 |
Zornitza Stark gene: SLC20A1 was added gene: SLC20A1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: SLC20A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SLC20A1 were set to 32850778; 27013921 Phenotypes for gene: SLC20A1 were set to Bladder-Exstrophy-Epispadias Complex (BEEC) Review for gene: SLC20A1 was set to GREEN gene: SLC20A1 was marked as current diagnostic Added comment: Three individuals and animal model supporting role of this gene in urinary tract and urorectal development. We have included on our CAKUT panel. Sources: Literature |
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| Fetal anomalies v1.95 | TRPM7 |
Zornitza Stark gene: TRPM7 was added gene: TRPM7 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: TRPM7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TRPM7 were set to 32503408; 31423533 Phenotypes for gene: TRPM7 were set to Cardiac arrhythmia, stillbirth Review for gene: TRPM7 was set to AMBER Added comment: I am not sure if genes linked to stillbirth belong on this panel. This gene encodes an ion channel expressed in the nervous and cardiac systems. It has previously been associated with ALS/dementia in the Guam population, but the variant in question, p.Thr1482Ile is present in >23,000 hets in gnomad, which is out of keeping for a rare Mendelian disorder. Note recent publication associating missense variants with cardiac arrhythmia and stillbirth, with some functional data provided to substantiate effect of variant on protein function but not necessarily establish gene-disease association. Sources: Literature |
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| Fetal anomalies v1.89 | SRY | Eleanor Williams Added comment: Comment on mode of inheritance: Changing mode of inheritance to "Other" has this gene is on the Y chromosome. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.74 | AMBRA1 |
Zornitza Stark gene: AMBRA1 was added gene: AMBRA1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: AMBRA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: AMBRA1 were set to 17589504; 32333458 Phenotypes for gene: AMBRA1 were set to Neural tube defects Review for gene: AMBRA1 was set to GREEN gene: AMBRA1 was marked as current diagnostic Added comment: 5 rare missense variants were identified in 6 cases from a neural tube defect cohort, and 4 (p.Thr80Met, p.Leu274Phe, p.Ser743Phe, and p.Met884Val) of them were functionally validated to affect autophagy regulation in vitro or zebrafish embryo development in vivo. There is also null mouse model with neural tube defects. Sources: Literature |
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| Fetal anomalies v1.73 | SHROOM4 |
Suzanne Drury gene: SHROOM4 was added gene: SHROOM4 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: SHROOM4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: SHROOM4 were set to 32565546 Phenotypes for gene: SHROOM4 were set to HP:0001274 Review for gene: SHROOM4 was set to AMBER Added comment: Reported in fetal case series of abnormal corpus callosum PMID:32565546. Case also had Blake's pouch cyst, Turner syndrome: mos46,X, psu idic(X)(p11.2)[19/45,X[6] Sources: Literature |
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| Fetal anomalies v1.73 | NUP88 |
Julia Baptista gene: NUP88 was added gene: NUP88 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: NUP88 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUP88 were set to PMID: 30543681 Phenotypes for gene: NUP88 were set to fetal akinesia Review for gene: NUP88 was set to RED Added comment: Bonnin et al reported biallelic variants in two unrelated families. A homozygous missense variant was identified in family A and the co-segregation data was supportive (tested 4 unaffected and 2 of the 4 affected fetuses). Compound heterozygous in-frame and nonsense variants were identified in the proband in family B (co-segregation studies in 2 unaffected sibs). The clinical features included fetal akinesia and arthrogryposis multiplex congenita. Polyhydramnios, muscle atrophy and dysmorphic features were also described. Sources: Literature |
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| Fetal anomalies v1.0 | ATP1A2 |
Zornitza Stark gene: ATP1A2 was added gene: ATP1A2 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: ATP1A2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATP1A2 were set to 30690204 Phenotypes for gene: ATP1A2 were set to hydrops fetalis; microcephaly; arthrogryposis; extensive cortical malformations Review for gene: ATP1A2 was set to AMBER gene: ATP1A2 was marked as current diagnostic Added comment: Three individuals from two unrelated families reported with balleliic LoF variants in this gene and hydrops/congenital abnormalities. Mouse model is perinatal lethal. This is a distinct phenotype from the mono allelic variants associated with alternating hemiplegia. Sources: Expert list |
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| Fetal anomalies v0.369 | BICD2 | Rebecca Foulger Phenotypes for gene: BICD2 were changed from PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291; arthrogryposis multiplex congenita (AMC); reduced fetal movements; hydrops fetalis to PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291; arthrogryposis multiplex congenita (AMC); reduced fetal movements; hydrops fetalis; Pterygium | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.368 | BICD2 | Rebecca Foulger Phenotypes for gene: BICD2 were changed from PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291 to PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291; arthrogryposis multiplex congenita (AMC); reduced fetal movements; hydrops fetalis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.367 | BICD2 | Rebecca Foulger commented on gene: BICD2: PMID:28635954 (Storbeck et al., 2017) describe 3 individuals of independent families with severe severe arthrogryposis multiplex congenita (AMC), respiratory insufficiency, and early lethality caused by three BICD2 variants (p.Arg694Cys, p.Gln194Arg and p.Cys542Trp, 2 of which are proven to be de novo). They also describe an asymptomatic women with subclinical findings with the previously described p.(Thr703Met) variant. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.367 | BICD2 | Rebecca Foulger commented on gene: BICD2: PMID:29274205 (Ahmed et al., 2018) report a stillborn female fetus (case 4) with pterygia and arthrogryposis with a heterozygous likely-pathogenic variant in BICD2. Phenotypes included an abnormal fetal position with fixed limbs, hydrops fetalis and polyhydramnios. A heterozygous p.Asn700Lys variant in BICD2 was revealed. However, compound het variants of unknown significance in AGRN were also identified, so the authors can not be certain that BICD2 is the causative variant. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.367 | BICD2 | Rebecca Foulger commented on gene: BICD2: PMID:27751653 (Ravenscroft et al., 2016) report two unrelated probands (a German male and a boy from a Welsh mother and NZ/European father) that presented in utero with reduced fetal movement. Both cases had arthrogryposis multiplex congenita (AMC) and hypotonia diagnosed at birth. The same missense de novo variant in BICD2 (p.Arg694Cys) was present in both probands. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.362 | KLF1 | Rebecca Foulger Phenotypes for gene: KLF1 were changed from ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE IV to ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE IV; Hydrops Fetalis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.343 | NMNAT2 | Rebecca Foulger commented on gene: NMNAT2: PMID:31132363, Huppke et al., 2019 report a homozygous missense variant (c.281C>T (T94M) in NMNAT2 in 2 siblings with childhood onset polyneuropathy with erythromelalgia: symptoms were first seen age 4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.342 | ANAPC1 | Rebecca Foulger commented on gene: ANAPC1: Added ANAPC1 to the Fetal anomalies panel and rated Green on approval from Anna de Burca and Richard Scott (Genomics England Clinical team). Note yet associated with a disorder in OMIM but evidence comes from PMID:31303264 (Ajeawung et al., 2019) where they report 10 individuals (7 families including 3 families of Amish ancestry) with Rothmund-Thomson Syndrome Type 1 and biallelic variants in ANAPC1. Phenotype includes skeletal abnormalities and short stature. All individuals carried an intronic splicing variant (NM_022662.3:c.2705−198C>T): in 3 Amish families plus individual 4, this intronic variant was found in a homozygous state. In the remaining families, the intronic variant was found in trans with one of three other LOF variants. Therefore sufficient cases to support a Green rating plus fetally-relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.338 | SLC35A2 | Rebecca Foulger Added comment: Comment on mode of inheritance: Gene2Phenotype currently records a 'monoallelic' MOI for SLC35A2 for 'CONGENITAL DISORDER OF GLYCOSYLATION'. Changed MOI from 'monoallelic' to 'XLD' because SLC35A2 is on the X-chromosome. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.318 | HRAS | Rebecca Foulger edited their review of gene: HRAS: Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.311 | DOK7 | Rebecca Foulger changed review comment from: This gene was added to the panel following review by Anna de Burca (Genomics England Clinical Team) and a Fetal Working Group call on July 19th 2019 with Lyn Chitty, Anna de Burca, Richard Scott, Rhiannon Mellis, Rebecca Foulger and Ellen McDonagh. Outcome of review: Rate Green because of finding in Normand et al., 2018 (PMID:30266093) plus additional case. Anna de Burca notes that DOK7 is Green on the Arthrogryposis panel - there seems to be quite variable severity but at least one case of arthrogryposis has been reported, so 2 cases if Normand et al included (doesnt decribe phenotype).; to: This gene was added to the panel following review by Anna de Burca (Genomics England Clinical Team) and a Fetal Working Group call on July 19th 2019 with Lyn Chitty, Anna de Burca, Richard Scott, Rhiannon Mellis, Rebecca Foulger and Ellen McDonagh. Outcome of review: Rate Green because of finding in Normand et al., 2018 (PMID:30266093) plus additional case. Anna de Burca notes that DOK7 is Green on the Arthrogryposis panel - there seems to be quite variable severity but at least one case of arthrogryposis has been reported, so 2 cases if Normand et al included (doesn't describe phenotype). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.311 | SCN2A | Rebecca Foulger edited their review of gene: SCN2A: Added comment: This gene was re-reviewed in a consistency check by Anna de Burca (Genomics England Clinical Team). Outcome of review: 2 reports of cortical malformations, one with ventriculomegaly: PMID:31204721,28254201. no reports of arthrogryposis. Plus finding in Petrovski et al., 2019 (PMID:30712878).; Changed rating: GREEN; Changed publications: 31204721, 28254201 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.311 | ACTA1 | Rebecca Foulger edited their review of gene: ACTA1: Added comment: This gene was reviewed by Anna de Burca (Genomics England Clinical Team) and at a Fetal Working Group call on July 19th 2019 by Lyn Chitty, Anna de Burca, Richard Scott, Rhiannon Mellis, Rebecca Foulger and Ellen McDonagh. Outcome of review: Rate Green because of finding in Normand et al., 2018 (PMID:30266093) plus additional case: Normand doesn't give any details of the clinical presentation. OMIM says the 'severe form' is associated with arthrogryposis. PMID:2724277 describes brothers with a heterozygous variant who presented antenatally with severe polyhydramnios and reduced fetal movements, postnatally were found to have arthrogryoposis. Parents were second cousins so might have been a missed second variant. PMID:11333380 reports 5 cases with heterozygous variants, some of which were born with severe hypotonia although the only antenatal feature was reduced fetal movements. Rate as Green for AD and AR as evident clinical variability.; Changed rating: GREEN; Changed publications: 2724277, 11333380 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.311 | SCN4A | Rebecca Foulger edited their review of gene: SCN4A: Added comment: This gene was re-reviewed in a consistency check by Anna de Burca (Genomics England Clinical Team), and at a Fetal Working Group call on July 19th 2019 by Lyn Chitty, Anna de Burca, Richard Scott, Rhiannon Mellis, Rebecca Foulger and Ellen McDonagh. Outcome of review: Green on arthrogryposis panel, and phenotypes include polyhydramnios, arthrogryposis (variable penetrance). Therefore promote from Red to Green.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.311 | DPAGT1 | Rebecca Foulger edited their review of gene: DPAGT1: Added comment: This gene was re-reviewed in a consistency check by Anna de Burca (Genomics England Clinical Team), and at a Fetal Working Group call on July 19th 2019 by Lyn Chitty, Anna de Burca, Richard Scott, Rhiannon Mellis, Rebecca Foulger and Ellen McDonagh. Outcome of review: Phenotype includes cataract, microcephaly, arthrogryposis. Therefore promote DPAGT1 from Red to Green.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.293 | KIAA1109 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green after agreement from Anna de Burca (Genomics England clinical team). KIAA1109 is Green on the 'Hydrocephalus' and 'Arthrogryposis' panels. Sufficient cases in OMIM to support association with Alkuraya-Kucinskas syndrome (MIM:617822) which includes arthrogryposis and brain abnormalities: severe cases are incompatible with life. Multiple ultrasounds abnormalities reported in PMIDs 30485398 and 29290337. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.290 | KIAA1109 | Rebecca Foulger commented on gene: KIAA1109: PMID:30485398: Filatova et al. 2019 report a Russian family with fetal anomalies detected upon ultrasound scans of three pregnancies. The first pregnancy resulted in a miscarriage. The second and third pregnancies were terminated because of ultrasound fetal abnormalities. In the third pregnancy, anomalies included bilateral ventriculomegaly, arthrogryposis (radial clubhand, bilateral clubfoot, flexed deformity of hip, knee and ankle joints), bilateral pyelectasis, increased thickness of the nuchal‐fold, hypoplastic and low set ears- Sanger sequencing revealed that the polymalformative fetus had compound heterozygous KIAA1109 variants. One of the dichorionic twins in the 4th pregnancy had similar phenotype and biallelic KIAA1109 variants (the healthy twin had only one variant c.1932‐3A>G). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.284 | MYRF | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Grey to Green. MYRF gene was added to the panel and reviewed by Julia Baptista. Sufficient cases to support MYRF variants causing Cardiac-urogenital syndrome (MIM:618280) from Pinz et al 2018 (PMID:29446546), Chitayat et al., (PMID:30070761), Qi et al.,2018 (PMID:30532227) and Rossetti et al., 2019 (PMID: 31069960). The phenotype is fetally-relevant (includes congenital diaphragmatic hernia/CDH, genital defects and cardiac defects) with multiple papers reporting detection in-utero: In both patients identified in Pinz et al 2018, anomalies were detected by ultrasound at 20 weeks gestation: mesocardia without other signs of heterotaxy (Patient 1), and a complex congenital heart defect with pericardial effusion (Patient 2). Chitayat et al., report a fetus with a novel de novo LOF variant in MYRF and a hypoplastic left heart and female external genitalia. In Rossetti et al., 2019, cardiac malformation and/or CDH was detected on a prenatal ultrasound. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.281 | MYRF | Rebecca Foulger Phenotypes for gene: MYRF were changed from congenital diaphragmatic hernia, cardiac defect, disorders of sexual development to Cardiac-urogenital syndrome, 618280; Congenital diaphragmatic hernia (CDH); Disorders of sex development (DSD) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.276 | PKD1 | Rebecca Foulger commented on gene: PKD1: PMID:23624871 (Gilbert et al., 2013) was added as a publication by Julia Baptista. The authors describe a male fetus with renal enlargement and oligohydramnios diagnosed at 27 weeks of gestation. This presentation resembled autosomal recessive PKD (ARPKD). Genetic analysis revealed a heterozygous truncating variant (p.Ser2788fs) in PKD1 inherited from the mother, and three unreported PKD1 variants inherited from the father. Although the authors don't exclude the possibility of a pathogenic variant in an additional gene, the paternally-inherited alleles support biallelic PKD1 alleles causing the fetal kidney anomalies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.273 | MYRF |
Julia Baptista gene: MYRF was added gene: MYRF was added to Fetal anomalies. Sources: Expert Review,Literature Mode of inheritance for gene: MYRF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MYRF were set to PMID: 30532227; 30985895; 31069960; 30070761; 29446546 ) Phenotypes for gene: MYRF were set to congenital diaphragmatic hernia, cardiac defect, disorders of sexual development Review for gene: MYRF was set to GREEN Added comment: Pinz et al. 2018 reported MYRF de novo pathogenic variants in 2 unrelated male infants with cardiac-urogenital syndrome (PMID: 29446546) Chitayat et al. (2018) reported one additional male fetus with complex congenital heart disease and severe urogenital malformations (PMID: 30070761). Qi et al. 2018 identified 7 patients from 6 families with heterozygous MYRF variants. All of the patients had cardiac defects. Urogenital defects were present in all 4 patients who were examined (PMID: 30532227). Rosetti et al 2019 described de novo heterozygous MYRF variants in three males. Congenital heart disease was presnet in 2/3 and diaphragmatic hernia in 2/3. Sources: Expert Review, Literature |
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| Fetal anomalies v0.273 | RIPK4 | Rebecca Foulger edited their review of gene: RIPK4: Added comment: Additional support for inclusion of gene on panel comes from Yates et al., 2017 (PMID:28425981, Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development). Yates et al., identified a heterozygous likely pathogenic variant in RIPK4 (plus a heterozygous VUS) in a case where the main ultrasound finding was Hydrops, diaphragmatic hernia, gracile ribs, contractures (Table 1). Additional VUS variants were reported in RSAD1 and PPAP2C.; Changed rating: AMBER; Changed phenotypes: Hydrops, diaphragmatic hernia, gracile ribs, contractures | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.273 | HRAS | Rebecca Foulger edited their review of gene: HRAS: Added comment: Additional support for inclusion of gene on panel comes from Yates et al., 2017 (PMID:28425981, Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development). Yates et al., identified a heterozygous variant in HRAS in a case where the main ultrasound finding was Hydrops (Table 1).; Changed rating: AMBER; Changed phenotypes: Hydrops | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.257 | HRAS | Rebecca Foulger Publications for gene: HRAS were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.247 | CNOT1 | Rebecca Foulger commented on gene: CNOT1: De Franco et al., 2019 (PMID:31006513) investigated a cohort of 107 individuals with pancreatic agenesis and definite/possible holoprosencephaly, and identified a heterozygous missense variant in CNOT1 (NM_016284.4; c.1603C>T (p.Arg535Cys)) in three unrelated individuals. The variant was de novo in two individuals, and was not present in the DNA sample from the third individual's father (maternal sample was unavailable). Mice required a homozygous variant to display a phenotype: in homozygous mice embryos (embryonically lethal) morphological abnormalities were apparent upon dissection including edema, a smaller dorsal pancreas, and exencephaly. The DDD study identified de novo CNOT1 variants in three individuals with developmental delay but none had holoprosencephaly, diabetes or pancreatic or neurological structural malformations. The authors therefore suggest that a mutation-specific mechanism rather than LOF is responsible for the pancreatic and holoprosencephaly phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.244 | HNRNPK | Rebecca Foulger commented on gene: HNRNPK: Au et al., 2018 (PMID:29904177) report prenatal presentation of Au-Kline syndrome: patient 9 presented prenatally with prune belly sequence, club feet, cystic kidneys associated with large cystic hygroma, pleural effusions and enlarged bladder. An additional 5 prenatal patients showed increased nuchal translucency and 5 patients had hydronephrosis. Congenital heart disease was reported for one patient prenatally. Agenesis of the corpus callosum was observed prenatally in one patient. Choroid plexus cysts, hyperechoic bowel, and ventriculomegaly have also been detected in ultrasound in single patients. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.244 | HNRNPK | Rebecca Foulger commented on gene: HNRNPK: Au-Kline syndrome is a multiple malformation syndrome associated with intellectual disability. Patients have facial dysmorphic features and frequently have skeletal and connective tissue anomalies, craniosynostosis, congenital heart malformations, and renal anomalies (PMID:29904177). Structural phenotypes reported in the literature include talipes and partial agenesis of corpus callosum. Au et al., 2018 (PMID:29904177) report prenatal presentation with 5 patients showing increased nuchal translucency and 5 patients had hydronephrosis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.237 | TUBB2A | Rebecca Foulger Added comment: Comment on list classification: Kept rating as Green following an assessment of evidence linking TUBB2A and cortical malformations. TUBB2A is Green on the PanelApp panel 'Malformations of cortical development'. Two cases are listed in OMIM from Cushion et al. (2014, PMID:24702957) plus further cases of Structural brain abnormalities in patients with TUBB2A variants are reported in Rodan et al., 2017 (PMID:27770045), Lee et al., 2014 (PMID:25326637) and Ejaz et al., 2017 (PMID:28840640). PMID:30016746 (2018) provides a summary. PMID:25326637 phenotypes include polymicrogyria and microcephaly (the age of onset of microcephaly is not noted). PMID:28840640 phenotypes include polymicrogyria and Arthrogryposis. Therefore sufficient evidence linking TUBB2A to cortical malformations that may be detected in a fetus. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.225 | MYT1 | Rebecca Foulger edited their review of gene: MYT1: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March and April 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: include on the Fetal anomalies panel as a Green gene. Additional notes from clinical review: There is no disorder in OMIM assocaited with MYT1, but Oculo-auriculo-vertebral spectrum (OAVS, also called Goldenhar) is described in two papers from same group- PMID:28612832 and PMID:27358179. There are 3 MYT1 variants from these 2 papers (2 missense, 1 nonsense) in OAVS patients so just meets evidence threshold. Caution was taken given the genetic heterogeneity and non-genetic factors associated with OAVS/Goldenhar. However on balance it was decided that the 3 literature variants are sufficient evidence for inclusion of MYT1 on the Fetal anomalies panel.; Changed rating: GREEN; Changed publications: 28612832, 27358179 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.224 | MYH6 | Rebecca Foulger Added comment: Comment on mode of inheritance: MYH6 had 'monoallelic' inheritance in the original PAGE list/DD-G2P for all three disorders. Changed mode of inheritance from 'monoallelic' to 'biallelic' following group expert clinical review by Lyn Chitty, Richard Scott, Anna de Burca and Rhiannon Mellis on 26th April 2019. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.222 | HCCS | Rebecca Foulger edited their review of gene: HCCS: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March and April 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: include on the Fetal anomalies panel as a Green gene. Additional notes from clinical review: Various fetal phenotypes on OMIM e.g. Ventricular septal defect (VSD) and diaphragmatic hernia.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.222 | ASAH1 | Rebecca Foulger edited their review of gene: ASAH1: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March and April 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: include on the Fetal anomalies panel as a Green gene. Additional notes from clinical review: Can (rarely) cause arthrogryposis.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.219 | MYH6 | Rebecca Foulger commented on gene: MYH6: In original PAGE file, mode of inheritance is 'Monoallelic' for all three disorders (ATRIAL SEPTAL DEFECT TYPE 3; CARDIOMYOPATHY DILATED TYPE 1EE; CARDIOMYOPATHY FAMILIAL HYPERTROPHIC TYPE 14). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.213 | POMK | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Fetally-relevant phenotype (hydrocephalus and macrocephaly detected in utero in patient in PMID:24925318) plus sufficient cases in literature/OMIM to support causation. Plus POMK is rated Green on PanelApp panels including Congenital muscular dystrophy/Hydrocephalus/Arthrogryposis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.208 | ZNF423 | Rebecca Foulger commented on gene: ZNF423: Chaki et al. (2012 PMID:22863007) identified a homozygous 2738C-T variant in the ZNF423 gene (P913L) in two Turkish siblings with with nephronophthisis-14 manifested as infantile-onset kidney disease, cerebellar vermis hypoplasia, and situs inversus. Heterozygous variants were found in two additional unrelated patients with Joubert syndrome. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.205 | ARL13B | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: ARL13B is on the Additional gene list in the PAGE paper (Lord et al., 2019, PMID:30712880) based on prenatal presentation of a phenotype in the literature. Sufficient (3 unrelated cases in OMIM (Pakistani, American, Tunisian) with homozygous or compound heterozygous variants in ARL13B in patients with a Joubert phenotype (from PMIDs 18674751 and 25138100). Plus functional evidence to support impairment of ARL13B protein function (PMID:29255182). Therefore sufficient evidence to support threshold for Green rating. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.198 | TTN |
Rebecca Foulger gene: TTN was added gene: TTN was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: TTN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TTN were set to 29575618; 28040389; 29691892 Phenotypes for gene: TTN were set to congenital titinopathy with arthrogryposis Review for gene: TTN was set to GREEN Added comment: TTN was reviewed on the DDG2P panel by Lucy Raymond with the comment: Biallelic LOF are congenital titinopathy with arthrogryposis and thus should be included. Rated 'possble' in DD-G2P for 'CAUSE OF EARLY-ONSET MYOPATHY WITH FATAL CARDIOMYOPATHY' but there are sufficient published cases of congenital titinopathies (with or without a cardiac component) for a Green rating. Therefore have added TTN to the Fetal anomalies panel as a Green gene following confirmation by Anna de Burca. Sources: Expert Review |
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| Fetal anomalies v0.198 | TTN |
Rebecca Foulger gene: TTN was added gene: TTN was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: TTN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TTN were set to 29575618; 28040389; 29691892 Phenotypes for gene: TTN were set to congenital titinopathy with arthrogryposis Review for gene: TTN was set to GREEN Added comment: TTN was reviewed on the DDG2P panel by Lucy Raymond with the comment: Biallelic LOF are congenital titinopathy with arthrogryposis and thus should be included. Rated 'possble' in DD-G2P for 'CAUSE OF EARLY-ONSET MYOPATHY WITH FATAL CARDIOMYOPATHY' but there are sufficient published cases of congenital titinopathies (with or without a cardiac component) for a Green rating. Therefore have added TTN to the Fetal anomalies panel as a Green gene following confirmation by Anna de Burca. Sources: Expert Review |
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| Fetal anomalies v0.185 | CHRNG | Rebecca Foulger edited their review of gene: CHRNG: Added comment: Additional evidence from PMID:30266093: AR/compound het variant identified in CHRNG from fetal exome sequencing in Normand et al., 2018 (Clinical exome sequencing for fetuses with ultrasound abnormalities and a suspected Mendelian disorder, PMID:30266093).; Changed publications: 30266093 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.184 | COL1A1 | Rebecca Foulger edited their review of gene: COL1A1: Added comment: Additional evidence from PMID:29595812:Variants identified in COL1A1 from fetal exome sequencing in Chandler et al., 2018 (Rapid diagnosis of fetal skeletal dysplasia using targeted exome sequencing, PMID:29595812). In one case, the variant is reported as a paternally-inherited VUS where no molecular diagnosis was made. In three cases the variants were De novo.; Changed publications: 29595812 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.183 | CHRNG | Rebecca Foulger edited their review of gene: CHRNG: Added comment: Additional evidence from PAGE study: Diagnostic Homozygous/Compound heterozygous variants identified in CHRNG from fetalexome sequencing inLord et al., 2019 (PMID:30712880).; Changed publications: 30712880 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.165 | TSHR |
Rebecca Foulger Source Expert Review Red was added to TSHR. Rating Changed from Green List (high evidence) to Red List (low evidence) |
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| Fetal anomalies v0.161 | CHRNA1 | Rebecca Foulger edited their review of gene: CHRNA1: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as a Green gene.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.161 | TSHR | Rebecca Foulger edited their review of gene: TSHR: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Phenotype is not fetally-relevant. Action taken: Demoted TSHR gene rating from Green to Red.; Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.161 | THRA | Rebecca Foulger edited their review of gene: THRA: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as a Green gene.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.153 | PYCR1 | Rebecca Foulger edited their review of gene: PYCR1: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as a Green gene. Additional notes from clinical review: An unpublished case presented with IUGR, Microcephaly, hydronephrosis, echogenic kidney, hypoplastic nasal bone. Long bones short and bowed, ambigious genitalia, megalourethra, thickened bladder wall. OMIM phenotypes include IUGR, microcephaly, long bone bowing and agenesis of the corpus callosum (ACC).; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.149 | ROR2 | Rebecca Foulger commented on gene: ROR2: In the original PAGE file, Mode of Inheritance is recorded as Biallelic for 'ROR2-RELATED DISORDERS AR', and Monoallelic for 'BRACHYDACTYLY, TYPE B1' and 'ROBINOW SYNDROME, AUTOSOMAL DOMINANT'. All three disorders have 'Confirmed' gene:disease associations with 'Loss of function' mode-of-pathogenicity. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.145 | GJB2 | Rebecca Foulger Added comment: Comment on mode of inheritance: In original PAGE file, inheritance was listed as biallelic for 'DEAFNESS AUTOSOMAL RECESSIVE TYPE 1A' and monoallelic for 'PALMOPLANTAR KERATODERMA WITH DEAFNESS', 'ICHTHYOSIS HYSTRIX-LIKE WITH DEAFNESS SYNDROME', 'VOHWINKEL SYNDROME' and 'BART-PUMPHREY SYNDROME'. Changed MOI to 'monoallelic' only following clinical review because the deafness phenotype alone is not detectable pre-natally. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.135 | GHR |
Rebecca Foulger Source Expert Review Red was added to GHR. Rating Changed from Green List (high evidence) to Red List (low evidence) |
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| Fetal anomalies v0.135 | CHRNA4 |
Rebecca Foulger Source Expert Review Red was added to CHRNA4. Rating Changed from Green List (high evidence) to Red List (low evidence) |
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| Fetal anomalies v0.135 | CHRDL1 |
Rebecca Foulger Source Expert Review Red was added to CHRDL1. Rating Changed from Green List (high evidence) to Red List (low evidence) |
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| Fetal anomalies v0.134 | HR | Rebecca Foulger edited their review of gene: HR: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as a Green gene.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.134 | GHR | Rebecca Foulger edited their review of gene: GHR: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Phenotype is not fetally-relevant. Additional notes from clinical review: Baby is normal size at birth and fails to grow afterwards, so not detectable prenatally. Action taken: Demoted GHR gene rating from Green to Red. ; Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.134 | CHST14 | Rebecca Foulger edited their review of gene: CHST14: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as Green. Additional notes from clinical review: Can cause Arthrogryposis.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.134 | CHRNG | Rebecca Foulger edited their review of gene: CHRNG: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as a Green gene.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.134 | CHRNA4 | Rebecca Foulger edited their review of gene: CHRNA4: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Phenotype is not fetally-relevant. Action taken: Demoted CHRNA4 gene rating from Green to Red.; Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.134 | CHRDL1 | Rebecca Foulger edited their review of gene: CHRDL1: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Phenotype is not fetally-relevant. Additional notes from clinical review: The megalocornea phenotype would not be detected pre-natally. Action taken: Demoted CHRDL1 gene rating from Green to Red.; Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.134 | C21orf2 | Rebecca Foulger edited their review of gene: C21orf2: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as Green. Additional notes from clinical review: Arthrogryposis reported amongst the phenotypes in OMIM.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.134 | C12orf65 | Rebecca Foulger edited their review of gene: C12orf65: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as Green. Additional notes from clinical review: Arthrogryposis reported amongst the phenotypes in OMIM.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.134 | CHRND | Rebecca Foulger edited their review of gene: CHRND: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as a Green gene.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.134 | HRAS | Rebecca Foulger edited their review of gene: HRAS: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as a Green gene.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.132 | ASCC1 |
Julia Baptista gene: ASCC1 was added gene: ASCC1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ASCC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ASCC1 were set to PMID: 26924529; 30327447; 28749478 Phenotypes for gene: ASCC1 were set to spinal muscular atrophy; arthrogryposis; fetal akinesia; hypotonia; contractures Review for gene: ASCC1 was set to GREEN gene: ASCC1 was marked as current diagnostic Added comment: Homozygous frameshift variant reported in two siblings from a Turkish family and one child from a Portuguese family affected with fetal akinesia, arthrogryposis, hypotonia, muscle weakness and congenital bone fractures. One further family reported with fetal akinesia and a homozygous splicing variant. Sources: Literature |
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| Fetal anomalies v0.123 | SGPL1 |
Rebecca Foulger gene: SGPL1 was added gene: SGPL1 was added to Fetal anomalies. Sources: Expert Review Green Mode of inheritance for gene: SGPL1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SGPL1 were set to Fetal hydrops; Nephrotic syndrome type 14, 617575 |
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| Fetal anomalies v0.110 | SMAD4 | Rebecca Foulger commented on gene: SMAD4: Changed rating to Amber to reflect DDG2P Disease confidence of 'both DD and IF' for JUVENILE POLYPOSIS/HEREDITARY HEMORRHAGIC TELANGIECTASIA SYNDROME; JUVENILE POLYPOSIS SYNDROME. SMAD4 is also rated 'confirmed' for MYHRE SYNDROME. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.110 | TIMM8A | Rebecca Foulger commented on gene: TIMM8A: Changed rating to Amber to reflect DDG2P Disease confidence of 'DD and IF' for JENSEN SYNDROME; MOHR-TRANEBJAERG SYNDROME. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.110 | MYH8 | Rebecca Foulger commented on gene: MYH8: Changed rating to Amber to reflect DDG2P Disease confidence of 'DD and IF' for CARNEY COMPLEX VARIANT; DISTAL ARTHROGRYPOSIS TYPE. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.92 | MAGEL2 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green following comment from Diedre Cilliers. Originally rated Amber based on multiple ratings for multiple disorders: rated as Confirmed for Schaaf-Yang syndrome in DDG2P, with sufficient (>3) cases to support causation. PMID:26365340 (Mejlachowicz et al 2015) report 3 fetuses with Schaaf-Yang syndrome manifested as arthrogryposis multiplex congenita (AMC) and death in utero, and Diedre Cilliers confirms that phenotype is fetally relevant. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.90 | MAGEL2 | Rebecca Foulger Phenotypes for gene: MAGEL2 were changed from Schaaf-Yang syndrome; ARTHROGRYPOSIS MULTIPLEX CONGENITA to Schaaf-Yang syndrome; ARTHROGRYPOSIS MULTIPLEX CONGENITA; Schaaf-Yang syndrome, 615547 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.74 | IFIH1 | Rebecca Foulger commented on gene: IFIH1: Communication from Deirdre Cilliers, Oxford University Hospitals (via email, February 2019) to support Green rating: Yes [IFIH1 should be on the Fetal anomalies panel]. Aicardi-Goutieres is often missed in the prenatal period as it is assumed that there is congenital infection present (even if testing negative). When reading through the cases in the literature, I think that later ultrasound scans in pregnancy might have identified some of the IFIH1 mutations in addition to the more commonly found TREX1. I have had two families in the past 2 years where I suggested the diagnosis in the prenatal period, although in one family with two affected pregnancies we never found the mutations. However, the phenotype is also clear on ultrasound scan as it looks like infection and the screen for this is negative. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.72 | ARCN1 | Rebecca Foulger commented on gene: ARCN1: Communication from Deirdre Cilliers, Oxford University Hospitals (via email, February 2019) to support Green rating: Yes [ARCN1 should be on the Fetal anomalies panel]. All [patients from PMID:27476655] have a degree of developmental delay, although most were mildy affected (useful for parents to have this information). Microcephaly and IUGR will be seen on ultrasound scan as well as structural anomalies, e.g. diaphragmatic hernia, VSD and severe micrognathia (some of these patients may need a paediatrician at birth for airway management as some have required tracheostomies). Cleft palate would likely be missed in most cases on ultrasound scan. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.71 | TPM2 | Rebecca Foulger Phenotypes for gene: TPM2 were changed from ARTHROGRYPOSIS, DISTAL, TYPE 1 to ARTHROGRYPOSIS, DISTAL, TYPE 1; Arthrogryposis multiplex congenita, distal, type 1, 108120; Arthrogryposis, distal, type 2B, 601680 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.70 | TPM2 | Rebecca Foulger commented on gene: TPM2: Communication from Deirdre Cilliers, Oxford University Hospitals (via email, February 2019) to support Green rating: Yes [TPM2 should be on the Fetal anomalies panel]. Distal arthrogryposis is seen relatively frequently on ultrasound scan. Often a diagnosis is of help as it gives information about the chance (or not) of learning difficulties when there is a diagnosis of arthrogryposis in the feta’s. The phenotype is also relatively straightforward to identify on ultrasound scan and this would make variant interpretation better. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.70 | CHRNA1 | Rebecca Foulger Publications for gene: CHRNA1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.69 | CHRNA1 | Rebecca Foulger Phenotypes for gene: CHRNA1 were changed from MULTIPLE PTERYGIUM SYNDROME LETHAL TYPE to MULTIPLE PTERYGIUM SYNDROME LETHAL TYPE; Multiple pterygium syndrome, lethal type, 253290 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.68 | CHRNA1 | Rebecca Foulger commented on gene: CHRNA1: Communication from Deirdre Cilliers, Oxford University Hospitals (via email, February 2019) to support Green rating: Yes [CHRNA1 should be on the Fetal anomalies panel]. The phenotype would be clear on ultrasound scan and variant interpretation would be easier because of this. In general, arthrogryposis can be variable, but the extent would be relatively obvious on scan and would be the reason for the test request. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.68 | CHRNA1 | Rebecca Foulger commented on gene: CHRNA1: Additional information to support Green rating: Rated Green on Arthrogryposis panel, and Green on 'Neuromuscular disorders' and 'Congenital myaesthenic syndrome' panels also. 2 unrelated cases in OMIM of CHRNA1 variants causing LETHAL-type multiple pterygium syndrome from PMID:18252226 (2008). Plus a 2018 paper (PMID:30177536) reporting a homozygous CHRNA1 variant in a child who had reduced fetal movements during pregnancy, polyhydramnios and arthrogryposis multiplex congenita (AMC). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.63 | LGI4 | Rebecca Foulger edited their review of gene: LGI4: Added comment: Additional details for change of rating from Amber ('probable' PAGE rating) to Green: Phenotype is fetally-relevant, and rated green on the 'Arthrogryposis', 'Congenital myopathy', 'Neuromuscular disorders' and 'Intellectual disability' panels. Sufficient evidence to support causation: 4 unrelated families with neurogenic arthrogryposis multiplex congenita with myelin defect (MIM:617468) and homozygous/compound heterozygous LGI4 variants from PMID:28318499 (Xue et al 2017).; Changed rating: GREEN; Changed publications: 28318499; Changed phenotypes: Arthrogryposis multiplex congenita, neurogenic, with myelin defect, 617468 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.63 | GLDN | Rebecca Foulger edited their review of gene: GLDN: Added comment: Additional details for change of rating from Amber ('probable' PAGE rating) to Green: Phenotype is fetally-relevant, and rated green on the 'Arthrogryposis' panel, and 4 families assocaited with 'Lethal congenital contracture syndrome 11, 617194' phenotype in OMIM, all from PMID:27616481 (Maluenda 2016).; Changed rating: GREEN; Changed publications: 27616481; Changed phenotypes: Lethal congenital contracture syndrome 11, 617194 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.63 | CNTNAP1 | Rebecca Foulger edited their review of gene: CNTNAP1: Added comment: Additional details for change of rating from Amber ('probable' PAGE rating) to Green: Phenotype is fetally-relevant, and rated green on the 'Arthrogryposis' V2.37 panel, and 4 families in OMIM associated with LETHAL CONGENITAL CONTRACTURE SYNDROME 7 (from PMID:24319099/Laquerriere et al 2014).; Changed rating: GREEN; Changed publications: 24319099; Changed phenotypes: Lethal congenital contracture syndrome 7, 616286 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.56 | WDR73 | Louise Daugherty Phenotypes for gene: WDR73 were changed from GALLOWAY-MOWAT SYNDROME: MICROCEPHALY AND STEROID-RESISTANT NEPHROTIC SYNDROME to GALLOWAY-MOWAT SYNDROME: MICROCEPHALY AND STEROID-RESISTANT NEPHROTIC SYNDROME; Galloway-Mowat syndrome 1, 251300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.31 | TPM2 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Rated Green on relevant V1 panel(s) PLUS phenotype (ARTHROGRYPOSIS, DISTAL, TYPE 1 ) appropriate for fetal panel, as noted by Helen Brittain and Anna de Burca (Genomics England Clinical team). 2 unrelated cases listed in OMIM for ARTHROGRYPOSIS disorders- TPM2 is Green on the Arthrogryposis panel based on these cases plus two Green reviews. Therefore reasonable to promote to Green on this fetal panel based on ARTHROGRYPOSIS phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.24 | LGI4 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Rated Green on relevant V1 panel(s) PLUS phenotype (ARTHROGRYPOSIS MULTIPLEX CONGENITA) appropriate for fetal panel, as noted by Helen Brittain and Anna de Burca (Genomics England Clinical team). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.21 | GLDN | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Rated Green on relevant V1 panel(s) PLUS phenotype (Lethal arthroogryposis) appropriate for fetal panel, as noted by Helen Brittain and Anna de Burca (Genomics England Clinical team). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.17 | CHRNA1 | Rebecca Foulger Classified gene: CHRNA1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.17 | CHRNA1 | Rebecca Foulger Gene: chrna1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | ZC4H2 | Rebecca Foulger commented on gene: ZC4H2: DDG2P rating in original PAGE list: Confirmed for ARTHROGRYPOSIS MULTIPLEX CONGENITA AND INTELLECTUAL DISABILITY. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | WNT7A | Rebecca Foulger commented on gene: WNT7A: DDG2P rating in original PAGE list: Confirmed for FUHRMANN SYNDROME and Confirmed for LIMB/PELVIS-HYPOPLASIA/APLASIA SYNDROME. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | TSHR | Rebecca Foulger commented on gene: TSHR: DDG2P rating in original PAGE list: Confirmed for HYPOTHYROIDISM, CONGENITAL, NONGOITROUS, 1 and Confirmed for HYPERTHYROIDISM, FAMILIAL GESTATIONAL. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | TPM2 | Rebecca Foulger commented on gene: TPM2: DDG2P rating in original PAGE list: Probable for ARTHROGRYPOSIS, DISTAL, TYPE 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | TMEM67 | Rebecca Foulger commented on gene: TMEM67: DDG2P rating in original PAGE list: Confirmed for COACH SYNDROM, Confirmed for MECKEL SYNDROME TYPE 3, Confirmed for JOUBERT SYNDROME TYPE 6 and Confirmed for NEPHRONOPHTHISIS TYPE 11. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | THRA | Rebecca Foulger reviewed gene: THRA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | SLC25A24 | Rebecca Foulger commented on gene: SLC25A24: DDG2P rating in original PAGE list: Confirmed for Gorlin-Chaudhry-Moss syndrome (GCMS); Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | SHROOM3 | Rebecca Foulger reviewed gene: SHROOM3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | RARB | Rebecca Foulger commented on gene: RARB: DDG2P rating in original PAGE list: Confirmed for MICROPHTHALMIA AND DIAPHRAGMATIC HERNIA and Confirmed for MICROPHTHALMIA AND DIAPHRAGMATIC HERNIA. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | PDE6H | Rebecca Foulger commented on gene: PDE6H: DDG2P rating in original PAGE list: Probable for ACHROMATOPSIA and Probable for RETINAL CONE DYSTROPHY 3 PDE6H. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | OSGEP | Rebecca Foulger commented on gene: OSGEP: DDG2P rating in original PAGE list: Probable for Nephrotic syndrome with primary microcephaly | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | NSDHL | Rebecca Foulger commented on gene: NSDHL: DDG2P rating in original PAGE list: Confirmed for CK SYNDROME and Confirmed for CONGENITAL HEMIDYSPLASIA WITH ICHTHYOSIFORM ERYTHRODERMA AND LIMB DEFECTS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | NEK8 | Rebecca Foulger commented on gene: NEK8: DDG2P rating in original PAGE list: Probable for NEPHRONOPHTHISIS 9 and Probable for RENAL-HEPATIC-PANCREATIC DYSPLASIA 2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | MYH9 | Rebecca Foulger commented on gene: MYH9: DDG2P rating in original PAGE list: Confirmed for DEAFNESS AUTOSOMAL DOMINANT TYPE 17, Confirmed for SEBASTIAN SYNDROME, Confirmed for MAY-HEGGLIN ANOMALY, Confirmed for EPSTEIN SYNDROME, Confirmed for FECHTNER SYNDROME, and Confirmed for MACROTHROMBOCYTOPENIA WITH PROGRESSIVE SENSORINEURAL DEAFNESS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | MYH3 | Rebecca Foulger commented on gene: MYH3: DDG2P rating in original PAGE list: Confirmed for DISTAL ARTHROGRYPOSIS TYPE 2B and Confirmed for DISTAL ARTHROGRYPOSIS TYPE 2A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | MECP2 | Rebecca Foulger commented on gene: MECP2: DDG2P rating in original PAGE list: Confirmed for RETT SYNDROME (RTT)[, Confirmed for MENTAL RETARDATION SYNDROMIC X-LINKED LUBS TYPE, Confirmed for MENTAL RETARDATION SYNDROMIC X-LINKED TYPE 13, Confirmed for CHROMOSOME XQ28 DUPLICATION SYNDROME, and Confirmed for ENCEPHALOPATHY NEONATAL SEVERE DUE TO MECP2 MUTATIONS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | MECOM | Rebecca Foulger commented on gene: MECOM: DDG2P rating in original PAGE list: Probable for Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | KLF1 | Rebecca Foulger commented on gene: KLF1: DDG2P rating in original PAGE list: Confirmed for ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE IV | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | IGF2 | Rebecca Foulger commented on gene: IGF2: DDG2P rating in original PAGE list: Confirmed for CHROMOSOME 11P15.5-RELATED RUSSELL-SILVER SYNDROME and Confirmed for BECKWITH-WIEDEMANN SYNDROME. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | HRAS | Rebecca Foulger commented on gene: HRAS: DDG2P rating in original PAGE list: Confirmed for COSTELLO SYNDROME and Confirmed for CONGENITAL MYOPATHY WITH EXCESS OF MUSCLE SPINDLES. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | HR | Rebecca Foulger commented on gene: HR: DDG2P rating in original PAGE list: Confirmed for ALOPECIA UNIVERSALIS and Confirmed for ATRICHIA WITH PAPULAR LESIONS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | GLE1 | Rebecca Foulger commented on gene: GLE1: DDG2P rating in original PAGE list: Confirmed for ARTHROGRYPOSIS, LETHAL, WITH ANTERIOR HORN CELL DISEASE | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | GJB2 | Rebecca Foulger commented on gene: GJB2: DDG2P rating in original PAGE list: Confirmed for DEAFNESS AUTOSOMAL RECESSIVE TYPE 1A, Confirmed for PALMOPLANTAR KERATODERMA WITH DEAFNESS, Confirmed for ICHTHYOSIS HYSTRIX-LIKE WITH DEAFNESS SYNDROME, Confirmed for VOHWINKEL SYNDROME and Confirmed for BART-PUMPHREY SYNDROME. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | GHR | Rebecca Foulger reviewed gene: GHR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | GATA6 | Rebecca Foulger commented on gene: GATA6: DDG2P rating in original PAGE list: Confirmed for ATRIOVENTRICULAR SEPTAL DEFECT 5, ATRIAL SEPTAL DEFECT 9, and Confirmed for PANCREATIC AGENESIS, DIAPHRAGMATIC HERNIA AND CONGENITAL HEART DEFECTS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | CHRNG | Rebecca Foulger reviewed gene: CHRNG: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | CHRND | Rebecca Foulger reviewed gene: CHRND: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | CHRNB2 | Rebecca Foulger commented on gene: CHRNB2: DDG2P rating in original PAGE list: Probable for CHRNB2-RELATED NOCTURNAL FRONTAL LOBE EPILEPSY, AUTOSOMAL DOMINANT and Probable NOCTURNAL FRONTAL LOBE EPILEPSY, AUTOSOMAL DOMINANT. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | CHRNA4 | Rebecca Foulger commented on gene: CHRNA4: DDG2P rating in original PAGE list: Confirmed for NOCTURNAL FRONTAL LOBE EPILEPSY TYPE 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | CHRNA1 | Rebecca Foulger reviewed gene: CHRNA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | CHRDL1 | Rebecca Foulger reviewed gene: CHRDL1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | ANKRD26 | Rebecca Foulger commented on gene: ANKRD26: DDG2P rating in original PAGE list: Probable for THROMBOCYTOPENIA 2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.7 | MYH8 | Rebecca Foulger commented on gene: MYH8: Rating in original PAGE file: 'both DD and IF' for CARNEY COMPLEX VARIANT and DISTAL ARTHROGRYPOSIS TYPE. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.5 | SMAD4 | Rebecca Foulger commented on gene: SMAD4: Multiple ratings in original PAGE file: rated as confirmed for MYHRE SYNDROME. Rated as both DD and IF for: JUVENILE POLYPOSIS/HEREDITARY HEMORRHAGIC TELANGIECTASIA SYNDROME and JUVENILE POLYPOSIS SYNDROME. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3 | HR | Rebecca Foulger reviewed gene: HR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3 | TSHR | Rebecca Foulger reviewed gene: TSHR: Rating: AMBER; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3 | CHRNA4 | Rebecca Foulger reviewed gene: CHRNA4: Rating: AMBER; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3 | HRAS | Rebecca Foulger reviewed gene: HRAS: Rating: AMBER; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3 | CHRNB2 | Rebecca Foulger reviewed gene: CHRNB2: Rating: AMBER; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | ZNF423 | Rebecca Foulger Added phenotypes Nephronophthisis 14 614844 for gene: ZNF423 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | ZC4H2 | Rebecca Foulger Added phenotypes ARTHROGRYPOSIS MULTIPLEX CONGENITA AND INTELLECTUAL DISABILITY for gene: ZC4H2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | ZC4H2 |
Rebecca Foulger gene: ZC4H2 was added gene: ZC4H2 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: ZC4H2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: ZC4H2 were set to ARTHROGRYPOSIS MULTIPLEX CONGENITA AND INTELLECTUAL DISABILITY |
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| Fetal anomalies v0.1 | WNT7A |
Rebecca Foulger gene: WNT7A was added gene: WNT7A was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: WNT7A was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: WNT7A were set to FUHRMANN SYNDROME |
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| Fetal anomalies v0.1 | WDR73 |
Rebecca Foulger gene: WDR73 was added gene: WDR73 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: WDR73 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: WDR73 were set to GALLOWAY-MOWAT SYNDROME: MICROCEPHALY AND STEROID-RESISTANT NEPHROTIC SYNDROME |
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| Fetal anomalies v0.1 | VPS33B |
Rebecca Foulger gene: VPS33B was added gene: VPS33B was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: VPS33B was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: VPS33B were set to ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 1 |
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| Fetal anomalies v0.1 | VIPAS39 |
Rebecca Foulger gene: VIPAS39 was added gene: VIPAS39 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: VIPAS39 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: VIPAS39 were set to ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 2 |
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| Fetal anomalies v0.1 | UROS |
Rebecca Foulger gene: UROS was added gene: UROS was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: UROS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: UROS were set to CONGENITAL ERYTHROPOIETIC PORPHYRIA |
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| Fetal anomalies v0.1 | TWIST1 |
Rebecca Foulger gene: TWIST1 was added gene: TWIST1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: TWIST1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: TWIST1 were set to SAETHRE-CHOTZEN SYNDROME |
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| Fetal anomalies v0.1 | TSHR | Rebecca Foulger Added phenotypes HYPERTHYROIDISM, FAMILIAL GESTATIONAL for gene: TSHR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | TSHR |
Rebecca Foulger gene: TSHR was added gene: TSHR was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: TSHR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: TSHR were set to HYPOTHYROIDISM, CONGENITAL, NONGOITROUS, 1 |
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| Fetal anomalies v0.1 | TSHB |
Rebecca Foulger gene: TSHB was added gene: TSHB was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: TSHB was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TSHB were set to HYPOTHRYOIDISM, CONGENITAL, NONGOITROUS 4 |
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| Fetal anomalies v0.1 | TPM2 |
Rebecca Foulger gene: TPM2 was added gene: TPM2 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: TPM2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: TPM2 were set to ARTHROGRYPOSIS, DISTAL, TYPE 1 |
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| Fetal anomalies v0.1 | TNNI2 |
Rebecca Foulger gene: TNNI2 was added gene: TNNI2 was added to Fetal anomalies. Sources: Expert Review Green,PAGE Additional Gene List Mode of inheritance for gene: TNNI2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: TNNI2 were set to Arthrogryposis multiplex congenita, distal, type 2B 601680 |
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| Fetal anomalies v0.1 | TMEM67 | Rebecca Foulger Added phenotypes NEPHRONOPHTHISIS TYPE 11 for gene: TMEM67 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | TIMM8A | Rebecca Foulger Added phenotypes MOHR-TRANEBJAERG SYNDROME for gene: TIMM8A | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | THRA |
Rebecca Foulger gene: THRA was added gene: THRA was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: THRA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: THRA were set to HYPOTHYROIDISM, CONGENITAL, NONGOITROUS, 6 |
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| Fetal anomalies v0.1 | TCTN3 |
Rebecca Foulger gene: TCTN3 was added gene: TCTN3 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: TCTN3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TCTN3 were set to MOHR-MAJEWSKI SYNDROME |
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| Fetal anomalies v0.1 | SON |
Rebecca Foulger gene: SON was added gene: SON was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: SON was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: SON were set to Intellectual Disability, Congenital Malformations, and Failure to Thrive |
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| Fetal anomalies v0.1 | SMAD4 |
Rebecca Foulger gene: SMAD4 was added gene: SMAD4 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: SMAD4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: SMAD4 were set to MYHRE SYNDROME |
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| Fetal anomalies v0.1 | SLC9A6 |
Rebecca Foulger gene: SLC9A6 was added gene: SLC9A6 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: SLC9A6 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: SLC9A6 were set to MENTAL RETARDATION SYNDROMIC X-LINKED CHRISTIANSON TYPE |
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| Fetal anomalies v0.1 | SLC6A9 |
Rebecca Foulger gene: SLC6A9 was added gene: SLC6A9 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: SLC6A9 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SLC6A9 were set to Glycine Encephalopathy with Arthrogryposis |
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| Fetal anomalies v0.1 | SLC25A24 |
Rebecca Foulger gene: SLC25A24 was added gene: SLC25A24 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: SLC25A24 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: SLC25A24 were set to Gorlin-Chaudhry-Moss syndrome (GCMS); Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction |
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| Fetal anomalies v0.1 | SHROOM3 |
Rebecca Foulger gene: SHROOM3 was added gene: SHROOM3 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: SHROOM3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: SHROOM3 were set to NEURAL TUBE DEFECT |
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| Fetal anomalies v0.1 | SEC23B |
Rebecca Foulger gene: SEC23B was added gene: SEC23B was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: SEC23B was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SEC23B were set to ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE II |
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| Fetal anomalies v0.1 | SCO2 |
Rebecca Foulger gene: SCO2 was added gene: SCO2 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: SCO2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SCO2 were set to FATAL INFANTILE CARDIOENCEPHALOMYOPATHY DUE TO CYTOCHROME C OXIDASE DEFICIENCY |
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| Fetal anomalies v0.1 | RBM8A |
Rebecca Foulger gene: RBM8A was added gene: RBM8A was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: RBM8A was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: RBM8A were set to THROMBOCYTOPENIA-ABSENT RADIUS SYNDROME |
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| Fetal anomalies v0.1 | RARB | Rebecca Foulger Added phenotypes MICROPHTHALMIA AND DIAPHRAGMATIC HERNIA for gene: RARB | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | RARB |
Rebecca Foulger gene: RARB was added gene: RARB was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: RARB was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: RARB were set to MICROPHTHALMIA AND DIAPHRAGMATIC HERNIA |
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| Fetal anomalies v0.1 | PRG4 |
Rebecca Foulger gene: PRG4 was added gene: PRG4 was added to Fetal anomalies. Sources: Expert Review Green,PAGE Additional Gene List Mode of inheritance for gene: PRG4 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PRG4 were set to Camptodactyly-arthropathy-coxa vara-pericarditis syndrome 208250 |
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| Fetal anomalies v0.1 | POR | Rebecca Foulger Added phenotypes Disordered steroidogenesis due to cytochrome P450 oxidoreductase 613571 for gene: POR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | PLCE1 |
Rebecca Foulger gene: PLCE1 was added gene: PLCE1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: PLCE1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PLCE1 were set to NEPHROTIC SYNDROME, TYPE 3 |
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| Fetal anomalies v0.1 | PIEZO2 |
Rebecca Foulger gene: PIEZO2 was added gene: PIEZO2 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: PIEZO2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: PIEZO2 were set to ARTHROGRYPOSIS, DISTAL, TYPE 3 |
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| Fetal anomalies v0.1 | PDE6H |
Rebecca Foulger gene: PDE6H was added gene: PDE6H was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: PDE6H was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PDE6H were set to ACHROMATOPSIA |
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| Fetal anomalies v0.1 | OSGEP |
Rebecca Foulger gene: OSGEP was added gene: OSGEP was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: OSGEP was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: OSGEP were set to Nephrotic syndrome with primary microcephaly |
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| Fetal anomalies v0.1 | NUP107 |
Rebecca Foulger gene: NUP107 was added gene: NUP107 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: NUP107 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NUP107 were set to EARLY-CHILDHOOD-ONSET STEROID-RESISTANT NEPHROTIC SYNDROME |
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| Fetal anomalies v0.1 | NSDHL | Rebecca Foulger Added phenotypes CONGENITAL HEMIDYSPLASIA WITH ICHTHYOSIFORM ERYTHRODERMA AND LIMB DEFECTS for gene: NSDHL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | NPHS2 |
Rebecca Foulger gene: NPHS2 was added gene: NPHS2 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: NPHS2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NPHS2 were set to NEPHROTIC SYNDROME, TYPE 2 |
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| Fetal anomalies v0.1 | NPHS1 |
Rebecca Foulger gene: NPHS1 was added gene: NPHS1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: NPHS1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NPHS1 were set to NEPHROTIC SYNDROME TYPE 1 |
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| Fetal anomalies v0.1 | NPHP4 |
Rebecca Foulger gene: NPHP4 was added gene: NPHP4 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: NPHP4 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NPHP4 were set to NEPHRONOPHTHISIS TYPE 4 |
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| Fetal anomalies v0.1 | NPHP3 | Rebecca Foulger Added phenotypes NEPHRONOPHTHISIS TYPE 3 for gene: NPHP3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | NPHP1 | Rebecca Foulger Added phenotypes NEPHRONOPHTHISIS TYPE 1 for gene: NPHP1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | NEK8 |
Rebecca Foulger gene: NEK8 was added gene: NEK8 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: NEK8 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NEK8 were set to NEPHRONOPHTHISIS 9 |
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| Fetal anomalies v0.1 | MYH9 | Rebecca Foulger Added phenotypes MACROTHROMBOCYTOPENIA WITH PROGRESSIVE SENSORINEURAL DEAFNESS for gene: MYH9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | MYH8 | Rebecca Foulger Added phenotypes DISTAL ARTHROGRYPOSIS TYPE for gene: MYH8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | MYH3 | Rebecca Foulger Added phenotypes DISTAL ARTHROGRYPOSIS TYPE 2A for gene: MYH3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | MYH3 |
Rebecca Foulger gene: MYH3 was added gene: MYH3 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: MYH3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: MYH3 were set to DISTAL ARTHROGRYPOSIS TYPE 2B |
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| Fetal anomalies v0.1 | MYBPC1 |
Rebecca Foulger gene: MYBPC1 was added gene: MYBPC1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE Additional Gene List Mode of inheritance for gene: MYBPC1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: MYBPC1 were set to Arthrogryposis, distal, type 1B 614335 |
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| Fetal anomalies v0.1 | MECP2 | Rebecca Foulger Added phenotypes CHROMOSOME XQ28 DUPLICATION SYNDROME for gene: MECP2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | MECOM |
Rebecca Foulger gene: MECOM was added gene: MECOM was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: MECOM was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: MECOM were set to Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia |
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| Fetal anomalies v0.1 | MAGEL2 | Rebecca Foulger Added phenotypes ARTHROGRYPOSIS MULTIPLEX CONGENITA for gene: MAGEL2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | LGI4 |
Rebecca Foulger gene: LGI4 was added gene: LGI4 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: LGI4 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: LGI4 were set to ARTHROGRYPOSIS MULTIPLEX CONGENITA |
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| Fetal anomalies v0.1 | KLF1 |
Rebecca Foulger gene: KLF1 was added gene: KLF1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: KLF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: KLF1 were set to ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE IV |
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| Fetal anomalies v0.1 | KANSL1 |
Rebecca Foulger gene: KANSL1 was added gene: KANSL1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: KANSL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: KANSL1 were set to CHROMOSOME 17Q21.31 MICRODELETION SYNDROME |
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| Fetal anomalies v0.1 | ITGA3 |
Rebecca Foulger gene: ITGA3 was added gene: ITGA3 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: ITGA3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ITGA3 were set to INTERSTITIAL LUNG DISEASE, NEPHROTIC SYNDROME, AND EPIDERMOLYSIS BULLOSA, CONGENITAL |
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| Fetal anomalies v0.1 | INVS |
Rebecca Foulger gene: INVS was added gene: INVS was added to Fetal anomalies. Sources: Expert Review Green,PAGE Additional Gene List Mode of inheritance for gene: INVS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: INVS were set to Nephronophthisis 2 602088 |
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| Fetal anomalies v0.1 | IGF2 |
Rebecca Foulger gene: IGF2 was added gene: IGF2 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: IGF2 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) Phenotypes for gene: IGF2 were set to CHROMOSOME 11P15.5-RELATED RUSSELL-SILVER SYNDROME |
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| Fetal anomalies v0.1 | HSD17B3 |
Rebecca Foulger gene: HSD17B3 was added gene: HSD17B3 was added to Fetal anomalies. Sources: Expert Review Green,PAGE Additional Gene List Mode of inheritance for gene: HSD17B3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: HSD17B3 were set to Pseudohermaphroditism, male, with gynecomastia 264300 |
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| Fetal anomalies v0.1 | HRAS | Rebecca Foulger Added phenotypes CONGENITAL MYOPATHY WITH EXCESS OF MUSCLE SPINDLES for gene: HRAS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | HRAS |
Rebecca Foulger gene: HRAS was added gene: HRAS was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: HRAS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: HRAS were set to COSTELLO SYNDROME |
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| Fetal anomalies v0.1 | HR | Rebecca Foulger Added phenotypes ATRICHIA WITH PAPULAR LESIONS for gene: HR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | HR |
Rebecca Foulger gene: HR was added gene: HR was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: HR was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: HR were set to ALOPECIA UNIVERSALIS |
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| Fetal anomalies v0.1 | HPGD |
Rebecca Foulger gene: HPGD was added gene: HPGD was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: HPGD was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: HPGD were set to CRANIOOSTEOARTHROPATHY |
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| Fetal anomalies v0.1 | GLIS2 |
Rebecca Foulger gene: GLIS2 was added gene: GLIS2 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: GLIS2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: GLIS2 were set to NEPHRONOPHTHISIS 7 |
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| Fetal anomalies v0.1 | GLE1 |
Rebecca Foulger gene: GLE1 was added gene: GLE1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: GLE1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: GLE1 were set to ARTHROGRYPOSIS, LETHAL, WITH ANTERIOR HORN CELL DISEASE |
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| Fetal anomalies v0.1 | GLDN |
Rebecca Foulger gene: GLDN was added gene: GLDN was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: GLDN was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: GLDN were set to Lethal arthroogryposis |
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| Fetal anomalies v0.1 | GJB2 | Rebecca Foulger Added phenotypes BART-PUMPHREY SYNDROME for gene: GJB2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | GHR |
Rebecca Foulger gene: GHR was added gene: GHR was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: GHR was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: GHR were set to PITUITARY DWARFISM II |
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| Fetal anomalies v0.1 | GATA6 | Rebecca Foulger Added phenotypes PANCREATIC AGENESIS, DIAPHRAGMATIC HERNIA AND CONGENITAL HEART DEFECTS for gene: GATA6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | ECEL1 |
Rebecca Foulger gene: ECEL1 was added gene: ECEL1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: ECEL1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ECEL1 were set to DISTAL ARTHROGRYPOSIS TYPE 5D |
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| Fetal anomalies v0.1 | CTNS | Rebecca Foulger Added phenotypes CYSTINOSIS LATE-ONSET JUVENILE OR ADOLESCENT NEPHROPATHIC TYPE for gene: CTNS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | CTNS | Rebecca Foulger Added phenotypes CYSTINOSIS NEPHROPATHIC TYPE for gene: CTNS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | CTNS |
Rebecca Foulger gene: CTNS was added gene: CTNS was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: CTNS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CTNS were set to CYSTINOSIS ADULT NON-NEPHROPATHIC TYPE |
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| Fetal anomalies v0.1 | CHRNG |
Rebecca Foulger gene: CHRNG was added gene: CHRNG was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: CHRNG was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CHRNG were set to MULTIPLE PTERYGIUM SYNDROME ESCOBAR VARIANT |
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| Fetal anomalies v0.1 | CHRND |
Rebecca Foulger gene: CHRND was added gene: CHRND was added to Fetal anomalies. Sources: Expert Review Green,PAGE Additional Gene List Mode of inheritance for gene: CHRND was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CHRND were set to Several associated, probably most relevant is lethal multiple pterygium syndrome 253290 |
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| Fetal anomalies v0.1 | CHRNB2 | Rebecca Foulger Added phenotypes NOCTURNAL FRONTAL LOBE EPILEPSY, AUTOSOMAL DOMINANT for gene: CHRNB2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | CHRNB2 |
Rebecca Foulger gene: CHRNB2 was added gene: CHRNB2 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: CHRNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: CHRNB2 were set to CHRNB2-RELATED NOCTURNAL FRONTAL LOBE EPILEPSY, AUTOSOMAL DOMINANT |
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| Fetal anomalies v0.1 | CHRNA4 |
Rebecca Foulger gene: CHRNA4 was added gene: CHRNA4 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: CHRNA4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: CHRNA4 were set to NOCTURNAL FRONTAL LOBE EPILEPSY TYPE 1 |
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| Fetal anomalies v0.1 | CHRNA1 |
Rebecca Foulger gene: CHRNA1 was added gene: CHRNA1 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: CHRNA1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CHRNA1 were set to MULTIPLE PTERYGIUM SYNDROME LETHAL TYPE |
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| Fetal anomalies v0.1 | CHRDL1 |
Rebecca Foulger gene: CHRDL1 was added gene: CHRDL1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: CHRDL1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: CHRDL1 were set to MEGALOCORNEA, X-LINKED |
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| Fetal anomalies v0.1 | CEP83 |
Rebecca Foulger gene: CEP83 was added gene: CEP83 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: CEP83 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CEP83 were set to INFANTILE NEPHRONOPHTHISIS AND INTELLECTUAL DISABILITY |
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| Fetal anomalies v0.1 | CEP164 |
Rebecca Foulger gene: CEP164 was added gene: CEP164 was added to Fetal anomalies. Sources: Expert Review Green,PAGE Additional Gene List Mode of inheritance for gene: CEP164 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CEP164 were set to Nephronophthisis 15 614845 |
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| Fetal anomalies v0.1 | CDAN1 |
Rebecca Foulger gene: CDAN1 was added gene: CDAN1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE Additional Gene List Mode of inheritance for gene: CDAN1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CDAN1 were set to Anemia, congenital dyserythropoietic, type I 224120 |
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| Fetal anomalies v0.1 | CD151 |
Rebecca Foulger gene: CD151 was added gene: CD151 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: CD151 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CD151 were set to NEPHROPATHY WITH PRETIBIAL EPIDERMOLYSIS BULLOSA AND DEAFNESS |
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| Fetal anomalies v0.1 | CCDC8 |
Rebecca Foulger gene: CCDC8 was added gene: CCDC8 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: CCDC8 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CCDC8 were set to THREE M SYNDROME 3 |
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| Fetal anomalies v0.1 | ASXL1 |
Rebecca Foulger gene: ASXL1 was added gene: ASXL1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: ASXL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: ASXL1 were set to BOHRING-OPITZ SYNDROME |
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| Fetal anomalies v0.1 | ANKRD26 |
Rebecca Foulger gene: ANKRD26 was added gene: ANKRD26 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: ANKRD26 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: ANKRD26 were set to THROMBOCYTOPENIA 2 |
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| Fetal anomalies v0.1 | ADAR |
Rebecca Foulger gene: ADAR was added gene: ADAR was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: ADAR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: ADAR were set to DYSCHROMATOSIS SYMMETRICA HEREDITARIA 1 |
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