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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
Fetal anomalies v1.984 GDF1 Arina Puzriakova Phenotypes for gene: GDF1 were changed from Congenital heart defects, multiple types; Right atrial isomerism (Ivemark) to Congenital heart defects, multiple types, 6, OMIM:613854; Right atrial isomerism (Ivemark), OMIM:208530
Fetal anomalies v1.917 CACNA1D Arina Puzriakova Phenotypes for gene: CACNA1D were changed from PRIMARY ALDOSTERONISM, SEIZURES, AND NEUROLOGIC ABNORMALITIES; SINOATRIAL NODE DYSFUNCTION AND DEAFNESS to Primary aldosteronism, seizures, and neurologic abnormalities, OMIM:615474
Fetal anomalies v1.863 ACO2 Sarah Leigh commented on gene: ACO2: New paper (34056600) describing ACO2 as a cause of autosomal dominant optic atrophy - update of inheritance needed.
Tom Cullup (Great Ormond Street Hospital), 17 Feb 2022
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 ATR Arina Puzriakova Tag for-review was removed from gene: ATR.
Fetal anomalies v1.836 ATR Arina Puzriakova commented on gene: ATR: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Fetal anomalies v1.835 ATR Arina Puzriakova Source Expert Review Green was added to ATR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v1.823 MYO5B Arina Puzriakova Phenotypes for gene: MYO5B were changed from MICROVILLUS INCLUSION DISEASE to Diarrhea 2, with microvillus atrophy, OMIM:251850
Fetal anomalies v1.822 TLL1 Ivone Leong gene: TLL1 was added
gene: TLL1 was added to Fetal anomalies. Sources: Expert Review Amber,Radboud University Medical Center, Nijmegen,Literature
Mode of inheritance for gene: TLL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TLL1 were set to 18830233; 30538173; 27418595; 10331975; 31570783
Phenotypes for gene: TLL1 were set to Atrial septal defect 6, OMIM:613087
Penetrance for gene: TLL1 were set to Complete
Fetal anomalies v1.809 AR Arina Puzriakova Phenotypes for gene: AR were changed from ANDROGEN INSENSITIVITY SYNDROME; SPINAL AND BULBAR MUSCULAR ATROPHY to ANDROGEN INSENSITIVITY SYNDROME
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
Fetal anomalies v1.683 ATAD3A Arina Puzriakova Phenotypes for gene: ATAD3A were changed from ATAD3A disorder - global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy; ATAD3A disorder - global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy; Harel-Yoon syndrome, 617183 to ATAD3A disorder - global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy; Harel-Yoon syndrome, OMIM:617183; Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal, OMIM:618810
Fetal anomalies v1.669 SCN7A Arina Puzriakova gene: SCN7A was added
gene: SCN7A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SCN7A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCN7A were set to 32732226
Phenotypes for gene: SCN7A were set to Holoprosencephaly
Review for gene: SCN7A was set to RED
Added comment: Novel candidate gene identified in a fetus with holoprosencephaly detected by ultrasound. Autopsy showed multiple congenital abnormalities including IUGR, microcephaly, bilateral, ablepharon, corpus callosum agenesis, myelomeningocele, tracheal atresia, absent nipples, unilateral simian crease, and hypoplastic phalanges. Compound heterozygous variants including a truncating variant were found by exome sequencing with concordant segregation.
Sources: Literature
Fetal anomalies v1.648 RFWD3 Rhiannon Mellis gene: RFWD3 was added
gene: RFWD3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RFWD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RFWD3 were set to PMID: 2869192
Phenotypes for gene: RFWD3 were set to Fanconi anaemia
Review for gene: RFWD3 was set to RED
Added comment: Fetally relevant phenotype but only one case reported in literature so far so await further cases.

(In the single reported case, the child had: intrauterine growth retardation, duodenal atresia, radial ray malformations, bilateral absent thumbs, small midface, ventriculomegaly, hypoplastic left kidney, and polysplenia. Brain MRI showed rarefied periventricular white matter, narrow corpus callosum, abnormal pituitary, and Chiari malformation type I)
Sources: Literature
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
Fetal anomalies v1.604 SIX6 Arina Puzriakova Phenotypes for gene: SIX6 were changed from Optic disc anomalies with retinal and/or macular dystrophy to Optic disc anomalies with retinal and/or macular dystrophy, OMIM:212550; Colobomatous optic disc-macular atrophy-chorioretinopathy syndrome, MONDO:0008927
Fetal anomalies v1.521 PTPN14 Arina Puzriakova Phenotypes for gene: PTPN14 were changed from CHOANAL ATRESIA AND LYMPHEDEMA to Choanal atresia and lymphedema, OMIM:613611; Lymphedema-posterior choanal atresia syndrome, MONDO:0013324
Fetal anomalies v1.428 ITGA8 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)

ITGA8 is also Green on the 'Unexplained paediatric onset end-stage renal disease v.1.2' GMS panel
Fetal anomalies v1.418 GSC Arina Puzriakova Phenotypes for gene: GSC were changed from Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities to Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities, OMIM:602471; Short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndrome, MONDO:0011227
Fetal anomalies v1.324 ATR Arina Puzriakova Phenotypes for gene: ATR were changed from SECKEL SYNDROME TYPE 1 to Seckel syndrome 1, OMIM:210600; Seckel syndrome 1, MONDO:0008869
Fetal anomalies v1.323 ATR Arina Puzriakova Classified gene: ATR as Amber List (moderate evidence)
Fetal anomalies v1.323 ATR Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.323 ATR Arina Puzriakova Gene: atr has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.322 ATR Arina Puzriakova Tag for-review tag was added to gene: ATR.
Fetal anomalies v1.275 MYL1 Arina Puzriakova Phenotypes for gene: MYL1 were changed from Myopathy, congenital, with fast-twitch (type II) fiber atrophy to Myopathy, congenital, with fast-twitch (type II) fiber atrophy, OMIM:618414; Congenital myopathy with reduced type 2 muscle fibers, MONDO:0034109
Fetal anomalies v1.229 ATR Rhiannon Mellis reviewed gene: ATR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Seckel syndrome 1, 210600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.214 GSC Rhiannon Mellis gene: GSC was added
gene: GSC was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: GSC was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GSC were set to Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities
Review for gene: GSC 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): Skeletal dysplasia
Sources: Expert list
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
Fetal anomalies v1.202 PTPN14 Rhiannon Mellis reviewed gene: PTPN14: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Choanal atresia and lymphedema; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
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
Fetal anomalies v1.171 NONO Arina Puzriakova Phenotypes for gene: NONO were changed from SYNDROMIC INTELLECTUAL DISABILITY to Left ventricular non-compaction cardiomyopathy (LVNC); Ventricular septal defect (VSD); Pulmonary stenosis; Atresia; Ebstein’s anomaly
Fetal anomalies v1.160 TRAPPC12 Arina Puzriakova Phenotypes for gene: TRAPPC12 were changed from Progressive Childhood Encephalopathy and Golgi Dysfunction to Hydrocephaly; Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, OMIM:617669; Early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome, MONDO:0044696
Fetal anomalies v1.158 TRAPPC12 Arina Puzriakova reviewed gene: TRAPPC12: Rating: AMBER; Mode of pathogenicity: None; Publications: 32347653, 28777934; Phenotypes: Hydrocephaly, Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, OMIM:617669, Early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome, MONDO:0044696; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.132 TBCD Arina Puzriakova Phenotypes for gene: TBCD were changed from Early-Onset Neurodegenerative Encephalopathy to Encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum, OMIM:617193; Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome, MONDO:0044646
Fetal anomalies v1.130 TRIP4 Arina Puzriakova Phenotypes for gene: TRIP4 were changed from Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures to Spinal muscular atrophy with congenital bone fractures 1, OMIM:616866; Prenatal-onset spinal muscular atrophy with congenital bone fractures, MONDO:0000209; Spinal muscular atrophy with congenital bone fractures 1, MONDO:0014806; ?Muscular dystrophy, congenital, Davignon-Chauveau type, OMIM:617066; Congenital muscular dystrophy-respiratory failure-skin abnormalities-joint hyperlaxity syndrome, MONDO:0014896
Fetal anomalies v1.100 CTNND1 Eleanor Williams reviewed gene: CTNND1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32196547; Phenotypes: Blepharocheilodontic syndrome 2, 617681, cardiovascular anomalies, developmental delay, choanal atresia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.97 SMN1 Eleanor Williams reviewed gene: SMN1: Rating: ; Mode of pathogenicity: None; Publications: 32644125, 32644120; Phenotypes: Spinal muscular atrophy; Mode of inheritance: None
Fetal anomalies v1.73 TMEM94 Rhiannon Mellis gene: TMEM94 was added
gene: TMEM94 was added to Fetal anomalies. Sources: Literature,Expert Review
Mode of inheritance for gene: TMEM94 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM94 were set to PMID: 30526868
Phenotypes for gene: TMEM94 were set to Intellectual developmental disorder with cardiac defects and dysmorphic facies
Review for gene: TMEM94 was set to GREEN
Added comment: Literature reports 10 patients from 6 unrelated families, and a mouse model PMID: 30526868

Reviewed with Prof Lyn Chitty for fetally relevant phenotype (Yes - Congenital heart malformations including: Atrial septal defect; Ventricular septal defect; Pulmonary hypoplasia; Pulmonary atresia; Tetralogy of Fallot; Double outlet right ventricle
Sources: Literature, Expert Review
Fetal anomalies v1.73 GDF1 Rhiannon Mellis gene: GDF1 was added
gene: GDF1 was added to Fetal anomalies. Sources: Literature,Expert Review
Mode of inheritance for gene: GDF1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GDF1 were set to PMID: 20413652; 28991257; 17924340
Phenotypes for gene: GDF1 were set to Congenital heart defects, multiple types; Right atrial isomerism (Ivemark)
Review for gene: GDF1 was set to GREEN
Added comment: Right atrial isomerism (AR): 5 sibs in one family PMID: 20413652; One unrelated individual with RAI, complex cardiac anomalies, abdominal heterotaxy and asplenia PMID: 28991257

Other varied CHD (including ToF, DORV, TGA) (AD): 8 unrelated individuals PMID 17924340

Reviewed for fetally relevant phenotype by Prof Lyn Chitty (Yes)

This gene appears on our local heterotaxy panel (NETRGL) and as Green on Panelapp Laterality disorders panel and Familial non-syndromic CHD panel.
Sources: Literature, Expert Review
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
Fetal anomalies v1.27 DHCR7 Rebecca Foulger commented on gene: DHCR7: PMID:31840946 (Schoner et al., 2020) performed autopsies and DHCR7 gene analyses in 8 fetuses suspected of having SLOS. 5/9 fetuses presented with classic SLOS features including 4 with atrial/atrioventricular septal defects and renal anomalies, and one with additional bilateral renal agenesis and a Dandy-Walker cyst. Two fetuses were mildly affected and two fetuses showed additional holoprosencephaly. DHCR7 variants were confirmed in cases 1-5 and 7.
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 v0.366 BICD2 Rebecca Foulger Phenotypes for gene: BICD2 were changed from PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE to PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291
Fetal anomalies v0.311 TUBB4A Rebecca Foulger edited their review of gene: TUBB4A: 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: Infantile onset hypomyelination with atrophy of basal ganglia & cerebellum- promote from Red to Green.; Changed rating: GREEN
Fetal anomalies v0.294 KIAA1109 Rebecca Foulger Added comment: Comment on mode of pathogenicity: The Mode of pathogenicity recorded in Gene2Phenotype for the disorder 'Brain atrophy, Dandy Walker and Contractures' is: All missense/in frame. However, as summarised in PMID:29290337 (Gueneau et al., 2018),
case subjects compatible with life carry missense variants but many of the more severely affected cases harbor homozygous or compound het truncating alleles. Therefore changed the Mode of pathogenicity back to default so LOF variants are captured.
Fetal anomalies v0.291 KIAA1109 Rebecca Foulger Phenotypes for gene: KIAA1109 were changed from Brain atrophy, Dandy Walker and Contractures to Brain atrophy, Dandy Walker and Contractures; Alkuraya-Kucinskas syndrome, 617822
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 v0.197 VPS53 Rebecca Foulger commented on gene: VPS53: Updated rating from Amber to Green to match confirmed Disease confidence rating in DD-G2P for new disorder (Progressive cerebella-cerebral atrophy type 2). Phenotype requires clinical review for fetal relevance.
Fetal anomalies v0.189 VPS53 Rebecca Foulger commented on gene: VPS53: VPS53 was added to the Fetal anomalies panel from the PAGE Additional Gene List (with rating: probable). New gene:disorder association added to DDG2P in March 2019: Progressive cerebella-cerebral atrophy type 2. DDG2P Disease confidence: confirmed. DDG2P mode of pathogenicity/mutation consequence: loss of function. DDG2P mode of inheritance: biallelic.
Fetal anomalies v0.189 VPS53 Rebecca Foulger Phenotypes for gene: VPS53 were changed from PONTOCEREBELLAR HYPOPLASIA, TYPE 2E 615851 to PONTOCEREBELLAR HYPOPLASIA, TYPE 2E 615851; Progressive cerebella-cerebral atrophy type 2
Fetal anomalies v0.183 ATRX Rebecca Foulger edited their review of gene: ATRX: Added comment: Additional evidence from PAGE study: Potentially clinically useful variant identified in this gene from fetalexome sequencing inLord et al., 2019 (PMID:30712880).; Changed publications: 30712880
Fetal anomalies v0.134 GJA1 Rebecca Foulger edited their review of gene: GJA1: 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: Include with monoallelic (Atrioventricular septal defects) and biallelic (Hypoplastic left heart syndrome 1) inheritance.; Changed rating: GREEN; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.134 CKAP2L Rebecca Foulger edited their review of gene: CKAP2L: 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: Phenotypes include cerebellar atrophy, Ventricular septal defect (VSD), Intrauterine growth restriction (IUGR) and microcephaly.; Changed rating: GREEN
Fetal anomalies v0.134 ATRX Rebecca Foulger edited their review of gene: ATRX: 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 ADSL Rebecca Foulger edited their review of gene: ADSL: 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: May present with cerebellar atrophy.; Changed rating: GREEN
Fetal anomalies v0.134 ACY1 Rebecca Foulger edited their review of gene: ACY1: 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: Include because the phenotype is severe, and Cerebellar atrophy was reported in 1 patient (OMIM Clinical Synopsis).; 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
Fetal anomalies v0.131 IGHMBP2 Rebecca Foulger Added comment: Comment on phenotypes: The disorder 'Neuronopathy, distal hereditary motor, type VI, 604320' is also called SMARD1 (SPINAL MUSCULAR ATROPHY WITH RESPIRATORY DISTRESS 1).
Fetal anomalies v0.131 IGHMBP2 Rebecca Foulger Phenotypes for gene: IGHMBP2 were changed from SPINAL MUSCULAR ATROPHY WITH RESPIRATORY DISTRESS 1 to SPINAL MUSCULAR ATROPHY WITH RESPIRATORY DISTRESS 1
Fetal anomalies v0.110 MYH6 Rebecca Foulger commented on gene: MYH6: Changed rating to Amber to reflect DDG2P Disease confidence of 'DD and IF' for ATRIAL SEPTAL DEFECT TYPE 3; CARDIOMYOPATHY DILATED TYPE 1EE; CARDIOMYOPATHY FAMILIAL HYPERTROPHIC TYPE 14.
Fetal anomalies v0.110 AR Rebecca Foulger commented on gene: AR: Changed rating to Amber to reflect DDG2P Disease confidence of 'DD and IF' for SPINAL AND BULBAR MUSCULAR ATROPHY; ANDROGEN INSENSITIVITY SYNDROME.
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 v0.63 TRIP4 Rebecca Foulger edited their review of gene: TRIP4: Added comment: Additional details for change of rating from Amber ('probable' PAGE rating) to Green: Phenotype is fetally-relevant, and rated green on the 'Paediatric motor neuronopathies' and 'Neuromuscular disorders' panels. Sufficient cases from one paper to support causation: 5 patients from 3 unrelated families (from Kosovo and Albania) with spinal muscular atrophy with congenital bone fractures-1 (MIM:616866) where Knierim et al. (2016, PMID:26924529) identified homozygous or compound het truncating variants in the TRIP4 gene.; Changed rating: GREEN; Changed publications: 26924529; Changed phenotypes: Spinal muscular atrophy with congenital bone fractures 1, 616866
Fetal anomalies v0.51 ATAD3A Rebecca Foulger Phenotypes for gene: ATAD3A were changed from ATAD3A disorder - global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy; ATAD3A disorder - global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy to ATAD3A disorder - global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy; ATAD3A disorder - global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy; Harel-Yoon syndrome, 617183
Fetal anomalies v0.34 ATAD3A Anna de Burca commented on gene: ATAD3A: PMID: 27640307 reports a recurrent de novo variant in ATAD3A in five unrelated individuals with developmental delay and hypotonia. Some individuals had peripheral neuropathy, optic atrophy and hypertrophic cardiomyopathy. A toxic gain of function mechanism was postulated. PMID: 28327206 reports an additional case with the same de novo variant. This individual had delayed motor development and hypotonia. PMID: 27640307 also reports a biallelic missense variant in siblings of distantly related parents with motor and speech delay, hypotonia, cerebellar atrophy, ataxia, seizures, muscle weakness, cataracts and optic nerve hypoplasia. There is insufficient evidence for this association at present. Therefore, this gene should be classified green with regard to monoallelic gain of function only.
Fetal anomalies v0.32 TRIP4 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Rated Green on relevant V1 panel(s) PLUS phenotype (Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures) appropriate for fetal panel, as noted by Helen Brittain and Anna de Burca (Genomics England Clinical team). Rated Green on 'Paediatric motor neuronopathies' panel based on sufficient cases, zebrafish model and Green review.
Fetal anomalies v0.9 TUBB4A Rebecca Foulger commented on gene: TUBB4A: DDG2P rating in original PAGE list: Confirmed for HYPOMYELINATION WITH ATROPHY OF THE BASAL GANGLIA AND CEREBELLUM
Fetal anomalies v0.9 TRPV4 Rebecca Foulger commented on gene: TRPV4: DDG2P rating in original PAGE list: Confirmed for SPONDYLOMETAPHYSEAL DYSPLASIA, KOZLOWSKI TYPE and Confirmed for METATROPIC DYSPLASIA.
Fetal anomalies v0.9 SLC39A8 Rebecca Foulger commented on gene: SLC39A8: DDG2P rating in original PAGE list: Confirmed for Intellectual Disability with Cerebellar Atrophy
Fetal anomalies v0.9 QARS Rebecca Foulger commented on gene: QARS: DDG2P rating in original PAGE list: Probable for MICROCEPHALY, PROGRESSIVE, SEIZURES, AND CEREBRAL AND CEREBELLAR ATROPHY
Fetal anomalies v0.9 NKX2-5 Rebecca Foulger commented on gene: NKX2-5: DDG2P rating in original PAGE list: Confirmed for ATRIAL SEPTAL DEFECT WITH ATRIOVENTRICULAR CONDUCTION DEFECTS, Confirmed for TETRALOGY OF FALLOT, and Confirmed for CONGENITAL HYPOTHYROIDISM NON-GOITROUS TYPE 5.
Fetal anomalies v0.9 MED17 Rebecca Foulger commented on gene: MED17: DDG2P rating in original PAGE list: Probable for MICROCEPHALY, POSTNATAL PROGRESSIVE, WITH SEIZURES AND BRAIN ATROPHY
Fetal anomalies v0.9 KIAA1109 Rebecca Foulger commented on gene: KIAA1109: DDG2P rating in original PAGE list: Probable for Brain atrophy, Dandy Walker and Contractures
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 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 EMC1 Rebecca Foulger commented on gene: EMC1: DDG2P rating in original PAGE list: Probable for monoallelic Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy and Probable for biallelic Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy.
Fetal anomalies v0.9 DYNC1H1 Rebecca Foulger commented on gene: DYNC1H1: DDG2P rating in original PAGE list: Confirmed for SPINAL MUSCULAR ATROPHY, LOWER EXTREMITY-PREDOMINANT, AD and Confirmed for SEVERE ID WITH NEURONAL MIGRATION DISORDER.
Fetal anomalies v0.9 CACNA1D Rebecca Foulger commented on gene: CACNA1D: DDG2P rating in original PAGE list: Probable for SINOATRIAL NODE DYSFUNCTION AND DEAFNESS and Probable for PRIMARY ALDOSTERONISM, SEIZURES, AND NEUROLOGIC ABNORMALITIES.
Fetal anomalies v0.9 BICD2 Rebecca Foulger commented on gene: BICD2: DDG2P rating in original PAGE list: Confirmed for PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE
Fetal anomalies v0.9 ATRX Rebecca Foulger reviewed gene: ATRX: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.9 ATR Rebecca Foulger reviewed gene: ATR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.9 ATP7A Rebecca Foulger commented on gene: ATP7A: DDG2P rating in original PAGE list: Confirmed for OCCIPITAL HORN SYNDROME, Confirmed for SPINAL MUSCULAR ATROPHY, DISTAL, X-LINKED 3 and Confirmed for MENKES DISEASE.
Fetal anomalies v0.9 ASAH1 Rebecca Foulger commented on gene: ASAH1: DDG2P rating in original PAGE list: Confirmed for FARBER LIPOGRANULOMATOSIS and Confirmed for SPINAL MUSCULAR ATROPHY ASSOCIATED WITH PROGRESSIVE MYOCLONIC EPILEPSY.
Fetal anomalies v0.7 MYH6 Rebecca Foulger commented on gene: MYH6: Rating in original PAGE file: 'both DD and IF' for ATRIAL SEPTAL DEFECT TYPE 3, CARDIOMYOPATHY DILATED TYPE 1EE and CARDIOMYOPATHY FAMILIAL HYPERTROPHIC TYPE 14.
Fetal anomalies v0.7 AR Rebecca Foulger commented on gene: AR: Rating in original PAGE file: 'both DD and IF' for both SPINAL AND BULBAR MUSCULAR ATROPHY and ANDROGEN INSENSITIVITY SYNDROME.
Fetal anomalies v0.1 UBA1 Rebecca Foulger gene: UBA1 was added
gene: UBA1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE Additional Gene List
Mode of inheritance for gene: UBA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: UBA1 were set to Spinal muscular atrophy, X-linked 2, infantile 301830
Fetal anomalies v0.1 TUBB4A Rebecca Foulger gene: TUBB4A was added
gene: TUBB4A was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: TUBB4A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TUBB4A were set to HYPOMYELINATION WITH ATROPHY OF THE BASAL GANGLIA AND CEREBELLUM
Fetal anomalies v0.1 TTC7A Rebecca Foulger gene: TTC7A was added
gene: TTC7A was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: TTC7A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTC7A were set to INTESTINAL ATRESIA, MULTIPLE
Fetal anomalies v0.1 TRPV4 Rebecca Foulger Added phenotypes METATROPIC DYSPLASIA for gene: TRPV4
Fetal anomalies v0.1 TRIP4 Rebecca Foulger gene: TRIP4 was added
gene: TRIP4 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: TRIP4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRIP4 were set to Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures
Fetal anomalies v0.1 TBX20 Rebecca Foulger gene: TBX20 was added
gene: TBX20 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: TBX20 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TBX20 were set to ATRIAL SEPTAL DEFECT TYPE 4
Fetal anomalies v0.1 TBCE Rebecca Foulger Added phenotypes Early-Onset Progressive Encephalopathy with Distal Spinal Muscular Atrophy for gene: TBCE
Fetal anomalies v0.1 SMN1 Rebecca Foulger gene: SMN1 was added
gene: SMN1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE Additional Gene List
Mode of inheritance for gene: SMN1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SMN1 were set to Spinal muscular atrophy 253550; Spinal muscular atrophy 271150; Spinal muscular atrophy 253400; Spinal muscular atrophy 253300
Fetal anomalies v0.1 SLC39A8 Rebecca Foulger gene: SLC39A8 was added
gene: SLC39A8 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: SLC39A8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC39A8 were set to Intellectual Disability with Cerebellar Atrophy
Fetal anomalies v0.1 SCYL1 Rebecca Foulger gene: SCYL1 was added
gene: SCYL1 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: SCYL1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SCYL1 were set to Episodes of Liver Failure, Peripheral Neuropathy, Cerebellar Atrophy, and Ataxia
Fetal anomalies v0.1 QARS Rebecca Foulger gene: QARS was added
gene: QARS was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: QARS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: QARS were set to MICROCEPHALY, PROGRESSIVE, SEIZURES, AND CEREBRAL AND CEREBELLAR ATROPHY
Fetal anomalies v0.1 PTPN14 Rebecca Foulger gene: PTPN14 was added
gene: PTPN14 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: PTPN14 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PTPN14 were set to CHOANAL ATRESIA AND LYMPHEDEMA
Fetal anomalies v0.1 NR2F1 Rebecca Foulger gene: NR2F1 was added
gene: NR2F1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: NR2F1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: NR2F1 were set to BOSCH-BOONSTRA OPTIC ATROPHY SYNDROME
Fetal anomalies v0.1 NKX2-5 Rebecca Foulger gene: NKX2-5 was added
gene: NKX2-5 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: NKX2-5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: NKX2-5 were set to ATRIAL SEPTAL DEFECT WITH ATRIOVENTRICULAR CONDUCTION DEFECTS
Fetal anomalies v0.1 MYH6 Rebecca Foulger gene: MYH6 was added
gene: MYH6 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: MYH6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: MYH6 were set to ATRIAL SEPTAL DEFECT TYPE 3
Fetal anomalies v0.1 MED17 Rebecca Foulger gene: MED17 was added
gene: MED17 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: MED17 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MED17 were set to MICROCEPHALY, POSTNATAL PROGRESSIVE, WITH SEIZURES AND BRAIN ATROPHY
Fetal anomalies v0.1 MECR Rebecca Foulger gene: MECR was added
gene: MECR was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: MECR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MECR were set to Childhood-Onset Dystonia and Optic Atrophy
Fetal anomalies v0.1 KIAA1109 Rebecca Foulger gene: KIAA1109 was added
gene: KIAA1109 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: KIAA1109 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: KIAA1109 were set to Brain atrophy, Dandy Walker and Contractures
Fetal anomalies v0.1 ITGB4 Rebecca Foulger gene: ITGB4 was added
gene: ITGB4 was added to Fetal anomalies. Sources: Expert Review Green,PAGE Additional Gene List
Mode of inheritance for gene: ITGB4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ITGB4 were set to Epidermolysis Bullosa with Pyloric Atresia. 226730
Fetal anomalies v0.1 ITGA6 Rebecca Foulger gene: ITGA6 was added
gene: ITGA6 was added to Fetal anomalies. Sources: Expert Review Green,PAGE Additional Gene List
Mode of inheritance for gene: ITGA6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ITGA6 were set to Epidermolysis Bullosa with Pyloric Atresia. 226730
Fetal anomalies v0.1 IGHMBP2 Rebecca Foulger gene: IGHMBP2 was added
gene: IGHMBP2 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: IGHMBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IGHMBP2 were set to SPINAL MUSCULAR ATROPHY WITH RESPIRATORY DISTRESS 1
Fetal anomalies v0.1 HR Rebecca Foulger Added phenotypes ATRICHIA WITH PAPULAR LESIONS for gene: HR
Fetal anomalies v0.1 GPAA1 Rebecca Foulger gene: GPAA1 was added
gene: GPAA1 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: GPAA1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GPAA1 were set to Developmental Delay, Epilepsy, Cerebellar Atrophy, and Osteopenia
Fetal anomalies v0.1 GATA6 Rebecca Foulger Added phenotypes ATRIAL SEPTAL DEFECT 9 for gene: GATA6
Fetal anomalies v0.1 GATA6 Rebecca Foulger gene: GATA6 was added
gene: GATA6 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: GATA6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: GATA6 were set to ATRIOVENTRICULAR SEPTAL DEFECT 5
Fetal anomalies v0.1 GATA4 Rebecca Foulger gene: GATA4 was added
gene: GATA4 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: GATA4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: GATA4 were set to ATRIAL SEPTAL DEFECT TYPE 2
Fetal anomalies v0.1 EMC1 Rebecca Foulger Added phenotypes Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy. for gene: EMC1
Fetal anomalies v0.1 EMC1 Rebecca Foulger gene: EMC1 was added
gene: EMC1 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: EMC1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: EMC1 were set to Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy.
Fetal anomalies v0.1 DYNC1H1 Rebecca Foulger gene: DYNC1H1 was added
gene: DYNC1H1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: DYNC1H1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: DYNC1H1 were set to SPINAL MUSCULAR ATROPHY, LOWER EXTREMITY-PREDOMINANT, AD
Fetal anomalies v0.1 CACNA1D Rebecca Foulger gene: CACNA1D was added
gene: CACNA1D was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: CACNA1D was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: CACNA1D were set to SINOATRIAL NODE DYSFUNCTION AND DEAFNESS
Fetal anomalies v0.1 BICD2 Rebecca Foulger gene: BICD2 was added
gene: BICD2 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: BICD2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: BICD2 were set to PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE
Fetal anomalies v0.1 ATRX Rebecca Foulger Added phenotypes ALPHA-THALASSEMIA MENTAL RETARDATION SYNDROME X-LINKED NON-DELETION TYPE for gene: ATRX
Fetal anomalies v0.1 ATRX Rebecca Foulger gene: ATRX was added
gene: ATRX was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: ATRX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: ATRX were set to MENTAL RETARDATION SYNDROMIC X-LINKED WITH HYPOTONIC FACIES SYNDROME TYPE 1
Fetal anomalies v0.1 ATR Rebecca Foulger gene: ATR was added
gene: ATR was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: ATR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ATR were set to SECKEL SYNDROME TYPE 1
Fetal anomalies v0.1 ATP7A Rebecca Foulger Added phenotypes SPINAL MUSCULAR ATROPHY, DISTAL, X-LINKED 3 for gene: ATP7A
Fetal anomalies v0.1 ATAD3A Rebecca Foulger Added phenotypes ATAD3A disorder - global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy for gene: ATAD3A
Fetal anomalies v0.1 ATAD3A Rebecca Foulger gene: ATAD3A was added
gene: ATAD3A was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: ATAD3A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: ATAD3A were set to ATAD3A disorder - global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy
Fetal anomalies v0.1 ASAH1 Rebecca Foulger Added phenotypes SPINAL MUSCULAR ATROPHY ASSOCIATED WITH PROGRESSIVE MYOCLONIC EPILEPSY for gene: ASAH1
Fetal anomalies v0.1 AR Rebecca Foulger gene: AR was added
gene: AR was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: AR was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: AR were set to SPINAL AND BULBAR MUSCULAR ATROPHY
Fetal anomalies v0.1 AP3B2 Rebecca Foulger gene: AP3B2 was added
gene: AP3B2 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: AP3B2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AP3B2 were set to Epileptic Encephalopathy with Optic Atrophy
Fetal anomalies v0.1 ACTC1 Rebecca Foulger gene: ACTC1 was added
gene: ACTC1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE Additional Gene List
Mode of inheritance for gene: ACTC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ACTC1 were set to 24461919
Phenotypes for gene: ACTC1 were set to Atrial septal defect 5 612794