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Fetal anomalies v3.122 KMT2B Arina Puzriakova Phenotypes for gene: KMT2B were changed from Complex early-onset dystonia to Dystonia 28, childhood-onset, OMIM:617284; Complex early-onset dystonia
Fetal anomalies v3.108 UQCRB Arina Puzriakova Phenotypes for gene: UQCRB were changed from MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX III DEFICIENCY, UQCRB-RELATED to Mitochondrial complex III deficiency, nuclear type 3, OMIM:615158
Fetal anomalies v3.98 ATP5O Sarah Leigh Phenotypes for gene: ATP5O were changed from Mitochondrial complex V (ATP synthase) deficiency to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 7, OMIM:620359
Fetal anomalies v3.78 GATB Arina Puzriakova changed review comment from: Confirmed with Stephanie Allen that there is sufficient evidence to classify this gene as Green. Additional comments: "One family with two affected compound heterozygotes reported; however, GATB, GATC & QRSL1 function together and this is supported by functional work, therefore classified as green when combining cases across the 3 genes."; to: Confirmed with Stephanie Allen that there is sufficient evidence to classify this gene as Green (9th May 2023). Additional comments: "One family with two affected compound heterozygotes reported; however, GATB, GATC & QRSL1 function together and this is supported by functional work, therefore classified as green when combining cases across the 3 genes."
Fetal anomalies v3.55 RMND1 Arina Puzriakova Phenotypes for gene: RMND1 were changed from ENCEPHALOPATHY ASSOCIATED WITH MULTIPLE OXIDATIVE PHOSPHORYLATION COMPLEX DEFICIENCIES AND A MITOCHONDRIAL TRANSLATION DEFECT; Combined oxidative phosphorylation deficiency 11, OMIM:614922 to Combined oxidative phosphorylation deficiency 11, OMIM:614922
Fetal anomalies v3.49 PET100 Arina Puzriakova Phenotypes for gene: PET100 were changed from MITOCHONDRIAL COMPLEX IV DEFICIENCY; Mitochondrial complex IV deficiency, nuclear type 12, OMIM:619055 to Mitochondrial complex IV deficiency, nuclear type 12, OMIM:619055
Fetal anomalies v3.41 NDUFS1 Arina Puzriakova Phenotypes for gene: NDUFS1 were changed from Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226; MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY; LEIGH SYNDROME to Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226
Fetal anomalies v3.36 NDUFB11 Arina Puzriakova Phenotypes for gene: NDUFB11 were changed from Linear skin defects with multiple congenital anomalies 3, OMIM:300952; Cardiomyopathy; Agenesis of corpus callosum (ACC) to ?Mitochondrial complex I deficiency, nuclear type 30, OMIM:301021; Linear skin defects with multiple congenital anomalies 3, OMIM:300952; Cardiomyopathy; Agenesis of corpus callosum (ACC)
Fetal anomalies v3.35 NDUFB10 Arina Puzriakova Phenotypes for gene: NDUFB10 were changed from Mitochondrial complex I deficiency, nuclear type 35, OMIM:619003; Mitochondrial complex I deficiency, nuclear type 35 , OMIM:619003 to Mitochondrial complex I deficiency, nuclear type 35, OMIM:619003
Fetal anomalies v3.8 UQCRFS1 Stephanie Allen reviewed gene: UQCRFS1: Rating: GREEN; Mode of pathogenicity: ; Publications: 31883641; Phenotypes: Mitochondrial complex III deficiency, nuclear type 10, OMIM:618775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 UQCC2 Stephanie Allen reviewed gene: UQCC2: Rating: AMBER; Mode of pathogenicity: ; Publications: 28804536, 24385928; Phenotypes: Mitochondrial complex III deficiency, nuclear type 7, OMIM:615824; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 SDHD Stephanie Allen reviewed gene: SDHD: Rating: RED; Mode of pathogenicity: ; Publications: 26008905; Phenotypes: Mitochondrial complex II deficiency, nuclear type 3, OMIM:619167; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 PET100 Stephanie Allen reviewed gene: PET100: Rating: GREEN; Mode of pathogenicity: ; Publications: 25293719; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 12, OMIM:619055; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 NDUFV2 Stephanie Allen reviewed gene: NDUFV2: Rating: AMBER; Mode of pathogenicity: ; Publications: 26008862; Phenotypes: Mitochondrial complex I deficiency, nuclear type 7, OMIM:618229; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 NDUFS1 Stephanie Allen reviewed gene: NDUFS1: Rating: GREEN; Mode of pathogenicity: ; Publications: 20382551, 31557978; Phenotypes: Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 NDUFC2 Stephanie Allen reviewed gene: NDUFC2: Rating: AMBER; Mode of pathogenicity: ; Publications: 32969598; Phenotypes: Mitochondrial complex I deficiency, nuclear type 36, OMIM:619170; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 NDUFB7 Stephanie Allen reviewed gene: NDUFB7: Rating: AMBER; Mode of pathogenicity: ; Publications: 33502047; Phenotypes: ?Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 NDUFB3 Stephanie Allen reviewed gene: NDUFB3: Rating: GREEN; Mode of pathogenicity: ; Publications: 27091925, 22277967; Phenotypes: Mitochondrial complex I deficiency, nuclear type 25, OMIM:618246; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 NDUFB11 Stephanie Allen reviewed gene: NDUFB11: Rating: GREEN; Mode of pathogenicity: ; Publications: 25772934; Phenotypes: ?Mitochondrial complex I deficiency, nuclear type 30, OMIM:301021, Linear skin defects with multiple congenital anomalies 3, OMIM:300952; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v3.8 NDUFB10 Stephanie Allen reviewed gene: NDUFB10: Rating: GREEN; Mode of pathogenicity: ; Publications: 31130284, 28040730; Phenotypes: Mitochondrial complex I deficiency, nuclear type 35, OMIM:619003; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 NDUFAF8 Stephanie Allen reviewed gene: NDUFAF8: Rating: GREEN; Mode of pathogenicity: ; Publications: 31866046; Phenotypes: Mitochondrial complex I deficiency, nuclear type 34, OMIM:618776; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 NDUFA6 Stephanie Allen reviewed gene: NDUFA6: Rating: GREEN; Mode of pathogenicity: ; Publications: 30245030; Phenotypes: Mitochondrial complex I deficiency, nuclear type 33, OMIM:618253; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 NDUFA12 Stephanie Allen reviewed gene: NDUFA12: Rating: RED; Mode of pathogenicity: ; Publications: 32341820, 35141356; Phenotypes: Mitochondrial complex I deficiency, nuclear type 23, OMIM:618244; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 MTFMT Stephanie Allen reviewed gene: MTFMT: Rating: GREEN; Mode of pathogenicity: ; Publications: 27393152, 30911575; Phenotypes: Combined oxidative phosphorylation deficiency 15, OMIM:614947, Mitochondrial complex I deficiency, nuclear type 27, OMIM:618248; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 COX14 Stephanie Allen reviewed gene: COX14: Rating: AMBER; Mode of pathogenicity: ; Publications: 22243966; Phenotypes: ?Mitochondrial complex IV deficiency, nuclear type 10 , OMIM:619053; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 COA6 Stephanie Allen reviewed gene: COA6: Rating: AMBER; Mode of pathogenicity: ; Publications: 22277967, 25339201; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 13, OMIM:616501; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 ATP5O Stephanie Allen reviewed gene: ATP5O: Rating: GREEN; Mode of pathogenicity: ; Publications: 35621276; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.7 PET100 Arina Puzriakova Added phenotypes Mitochondrial complex IV deficiency, nuclear type 12, OMIM:619055 for gene: PET100
Fetal anomalies v3.7 NDUFB10 Arina Puzriakova Added phenotypes Mitochondrial complex I deficiency, nuclear type 35, OMIM:619003 for gene: NDUFB10
Fetal anomalies v3.7 NDUFS1 Arina Puzriakova Source Expert Review Amber was added to NDUFS1.
Added phenotypes Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226 for gene: NDUFS1
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Fetal anomalies v3.7 SDHD Arina Puzriakova gene: SDHD was added
gene: SDHD was added to Fetal anomalies. Sources: Expert Review Red
Mode of inheritance for gene: SDHD was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SDHD were set to Mitochondrial complex II deficiency, nuclear type 3, OMIM:619167
Fetal anomalies v3.7 NDUFA12 Arina Puzriakova gene: NDUFA12 was added
gene: NDUFA12 was added to Fetal anomalies. Sources: Expert Review Red
Mode of inheritance for gene: NDUFA12 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFA12 were set to Mitochondrial complex I deficiency, nuclear type 23, OMIM:618244
Fetal anomalies v3.7 UQCRFS1 Arina Puzriakova gene: UQCRFS1 was added
gene: UQCRFS1 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: UQCRFS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UQCRFS1 were set to Mitochondrial complex III deficiency, nuclear type 10, OMIM:618775
Fetal anomalies v3.7 UQCC2 Arina Puzriakova gene: UQCC2 was added
gene: UQCC2 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: UQCC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UQCC2 were set to Mitochondrial complex III deficiency, nuclear type 7, OMIM:615824
Fetal anomalies v3.7 NDUFV2 Arina Puzriakova gene: NDUFV2 was added
gene: NDUFV2 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: NDUFV2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFV2 were set to Mitochondrial complex I deficiency, nuclear type 7, OMIM:618229
Fetal anomalies v3.7 NDUFC2 Arina Puzriakova gene: NDUFC2 was added
gene: NDUFC2 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: NDUFC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFC2 were set to Mitochondrial complex I deficiency, nuclear type 36, OMIM:619170
Fetal anomalies v3.7 NDUFB7 Arina Puzriakova gene: NDUFB7 was added
gene: NDUFB7 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: NDUFB7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFB7 were set to ?Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135
Fetal anomalies v3.7 NDUFB3 Arina Puzriakova gene: NDUFB3 was added
gene: NDUFB3 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: NDUFB3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFB3 were set to Mitochondrial complex I deficiency, nuclear type 25, OMIM:618246
Fetal anomalies v3.7 NDUFAF8 Arina Puzriakova gene: NDUFAF8 was added
gene: NDUFAF8 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: NDUFAF8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFAF8 were set to Mitochondrial complex I deficiency, nuclear type 34, OMIM:618776
Fetal anomalies v3.7 NDUFA6 Arina Puzriakova gene: NDUFA6 was added
gene: NDUFA6 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: NDUFA6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFA6 were set to Mitochondrial complex I deficiency, nuclear type 33, OMIM:618253
Fetal anomalies v3.7 MTFMT Arina Puzriakova gene: MTFMT was added
gene: MTFMT was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: MTFMT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MTFMT were set to Combined oxidative phosphorylation deficiency 15, OMIM:614947; Mitochondrial complex I deficiency, nuclear type 27, OMIM:618248
Fetal anomalies v3.7 COX14 Arina Puzriakova gene: COX14 was added
gene: COX14 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: COX14 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COX14 were set to ?Mitochondrial complex IV deficiency, nuclear type 10 , OMIM:619053
Fetal anomalies v3.7 COA6 Arina Puzriakova gene: COA6 was added
gene: COA6 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: COA6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COA6 were set to Mitochondrial complex IV deficiency, nuclear type 13, OMIM:616501
Fetal anomalies v3.7 ATP5O Arina Puzriakova gene: ATP5O was added
gene: ATP5O was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: ATP5O was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ATP5O were set to Mitochondrial complex V (ATP synthase) deficiency
Fetal anomalies v3.5 CDX2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Dmitrijs Rots (RadboudUMC). At least 8 unrelated families reported with de novo or inherited pathogenic variants in CDX2. Phenotypic findings comprise a broad spectrum of caudal abnormalities including defects of the uro‐recto‐genital tract, vertebrae, and the limbs. Cdx2 mutant mice show a variable phenotype that is comparable to that of patients (including imperforate anus, sirenomelia, posterior vertebral truncations, and bladder anomalies).

Overall there is sufficient evidence to promote this gene to Green at the next GMS panel update.
Fetal anomalies v3.1 AARS2 Patrick Campbell gene: AARS2 was added
gene: AARS2 was added to Fetal anomalies. Sources: NHS GMS
Mode of inheritance for gene: AARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AARS2 were set to 30819764
Phenotypes for gene: AARS2 were set to fetal hydrops; polyhydramnios; pulmonary effusion; cardiomyopathy
Penetrance for gene: AARS2 were set to Complete
Mode of pathogenicity for gene: AARS2 was set to Other
Review for gene: AARS2 was set to GREEN
Added comment: This gene is not on R21. It can cause fetal phenotype and early neonatal death with bi-allelic variants. We had a fetus present locally with fetal hydrops from around 28 weeks. The result was discovered on whole genome sequencing after miscarriage (R14). It would not have been identified on R21 for fetal anomalies. The local finding of presentation antenatally is corroborated by recent publication (PMID 30819764) with a case showing polyhydramnios and nonimmune hydrops, with small pulmonary effusions and significant ascites first detected at 35 wk of pregnancy.
Consideration should be given to adding the gene to R21.
Sources: NHS GMS
Fetal anomalies v2.8 TUBB2B Arina Puzriakova Phenotypes for gene: TUBB2B were changed from POLYMICROGYRIA ASYMMETRIC to Cortical dysplasia, complex, with other brain malformations 7, OMIM:610031
Fetal anomalies v2.4 COX10 Arina Puzriakova Phenotypes for gene: COX10 were changed from MITOCHONDRIAL COMPLEX IV DEFICIENCY; LEIGH SYNDROME to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046
Fetal anomalies v1.948 NDUFB10 Arina Puzriakova Phenotypes for gene: NDUFB10 were changed from Mitochondrial complex I deficiency to Mitochondrial complex I deficiency, nuclear type 35 , OMIM:619003
Fetal anomalies v1.900 NDUFB10 Rhiannon Mellis gene: NDUFB10 was added
gene: NDUFB10 was added to Fetal anomalies. Sources: Expert Review,Literature
Mode of inheritance for gene: NDUFB10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFB10 were set to PMID: 31130284; 28040730
Phenotypes for gene: NDUFB10 were set to Mitochondrial complex I deficiency
Review for gene: NDUFB10 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 other panels (Amber/Red because only 1 case reported, with functional studies). Causes Mitochondrial complex 1 deficiency.
One fetal case reported by Monies et al 2019 (PMID: 31130284) with Non-immune hydrops fetalis and died after birth.
The previous reported case on OMIM (from PMID: 28040730) was a female infant with IUGR, hydrops, lung hypoplasia and fetal cardiomyopathy - neonatal death with rapidly progressive lactic acidosis and PM found decreased complex 1 activity in skeletal muscle, heart, liver. Previous child of parents also had hydrops and died on day 1 of life.
Sources: Expert Review, Literature
Fetal anomalies v1.899 TMEM70 Arina Puzriakova Phenotypes for gene: TMEM70 were changed from MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 2 to IUGR; Oligohydramnios; Anhydramnios; Cardiomyopathy
Fetal anomalies v1.880 NEXN Rhiannon Mellis gene: NEXN was added
gene: NEXN was added to Fetal anomalies. Sources: Literature,Expert Review
Mode of inheritance for gene: NEXN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEXN were set to PMID: 32058062; PMID: 33027564
Phenotypes for gene: NEXN were set to Cardiomyopathy
Review for gene: NEXN was set to AMBER
Added comment: This gene and phenotype were reviewed during a meeting on 21st July 2022 between representatives of the North Thames and Central & South R21 testing GLHs.
Clinical review and curation was performed by Lyn Chitty, Alison Male, Rhiannon Mellis (North Thames GLH), and Stephanie Allen, Denise Williams, Esther Kinning and Anna de Burca (Central & South GLH).

Outcome of review: Gene usually causes adult-onset AD cardiomyopathy. However, there may be a fetally relevant phenotype with biallelic variants. Support adding to the Fetal anomalies panel as an Amber gene, pending more evidence of fetal phenotype (only 2 reported unrelated cases to date).

Currently rated Green on the following other PanelApp panel(s): Cardiomyopathy (dilated)

Details of review: The fetal case in Sparks et al (PMID: 33027564) had pericardial effusion, ascites, cardiomegaly, dilation and hypertrophy of cardiac ventricles, hypoplastic and dysplastic aortic valve, diminished systolic function, fetal growth restriction, and was stillborn. 2 NEXN variants found in the fetus (1 mat inherited, 1 de novo) but unable to confirm phase.
The fetal case in Rinaldi et al 2021 (PMID: 32058062) had Cardiomegaly, low contractility/outflow, fibroelastosis of right ventricle. The fetus was compound het for NEXN variants and parents were both unaffected het with normal echos. They'd had one previous pregnancy with same phenotype.
Sources: Literature, Expert Review
Fetal anomalies v1.874 TUBG1 Arina Puzriakova Phenotypes for gene: TUBG1 were changed from Posteriorly predominant pachygyria and severe microcephaly to Cortical dysplasia, complex, with other brain malformations 4, OMIM:615412
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
Fetal anomalies v1.865 CYP11A1 Arina Puzriakova Added comment: Comment on mode of inheritance: Homozygous, compound heterozygous, and heterozygous (although most rare) variants in the CYP11A1 gene have all been associated with disease. Therefore, MOI should be updated to 'Both mono- and biallelic' at the next GMS panel update.
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
Fetal anomalies v1.849 BRIP1 Arina Puzriakova Phenotypes for gene: BRIP1 were changed from FANCONI ANEMIA, COMPLEMENTATION GROUP J to Fanconi anemia, complementation group J, OMIM:609054
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 v1.847 PEX6 Sarah Leigh Phenotypes for gene: PEX6 were changed from PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 4; ZELLWEGER SYNDROME to Heimler syndrome 2, OMIM:616617; Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862; Peroxisome biogenesis disorder 4B, OMIM:614863
Fetal anomalies v1.845 PEX6 Sarah Leigh Added comment: Comment on mode of inheritance: The Q1_22_MOI tag has been added to this gene. The mode of inheritance for PEX6 should be set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.
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 v1.811 CLPB Arina Puzriakova Added comment: Comment on mode of inheritance: Association between biallelic variants and disease is well established, with more than 35 affected individuals reported. Recently, Wortmann et al. 2021 (PMID: 34140661) published six unrelated individuals with one of four different de novo monoallelic missense variants in CLPB. The phenotype strongly overlapped with that observed in the recessive disease. No prenatal findings were specifically mentioned but given the otherwise comparable clinical presentations, monoallelic inheritance may also be of relevance to this panel. Therefore, will flag this for further GMS review.
Fetal anomalies v1.803 CNBP_CCTG Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to support the gene-disease association but setting rating to Red as currently the performance of the pipeline for this STR is very poor as it is located in a complex locus.
Fetal anomalies v1.784 PRRX1 Arina Puzriakova Phenotypes for gene: PRRX1 were changed from Agnathia-otocephaly complex to Agnathia-otocephaly complex, OMIM:202650
Fetal anomalies v1.749 PRRX1 Rhiannon Mellis gene: PRRX1 was added
gene: PRRX1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PRRX1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PRRX1 were set to 21294718; 22211708; 22674740; 23444262
Phenotypes for gene: PRRX1 were set to Agnathia-otocephaly complex
Review for gene: PRRX1 was set to GREEN
Added comment: At least 4 unrelated cases reported with agnathia-otocephaly complex
Sources: Literature
Fetal anomalies v1.746 CYP11A1 Arina Puzriakova Phenotypes for gene: CYP11A1 were changed from Adrenal insufficiency, congenital, with 46XY sex reversal, partial or complete 613743 to Adrenal insufficiency, congenital, with 46XY sex reversal, partial or complete, OMIM:613743
Fetal anomalies v1.736 LRIT3 Zornitza Stark reviewed gene: LRIT3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Night blindness, congenital stationary (complete), 1F, autosomal recessive 615058; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.724 BHLHA9 Eleanor Williams Phenotypes for gene: BHLHA9 were changed from ?Camptosynpolydactyly, complex, OMIM:607539; Syndactyly, mesoaxial synostotic, with phalangeal reduction, OMIM:609432SPLIT HAND AND FOOT MALFORMATION; MESOAXIAL SYNOSTOTIC SYNDACTYLY WITH PHALANGEAL REDUCTION, MALIK-PERCIN TYPE to ?Camptosynpolydactyly, complex, OMIM:607539; Syndactyly, mesoaxial synostotic, with phalangeal reduction, OMIM:609432; SPLIT HAND AND FOOT MALFORMATION; MESOAXIAL SYNOSTOTIC SYNDACTYLY WITH PHALANGEAL REDUCTION, MALIK-PERCIN TYPE
Fetal anomalies v1.723 BHLHA9 Eleanor Williams Phenotypes for gene: BHLHA9 were changed from SPLIT HAND AND FOOT MALFORMATION; MESOAXIAL SYNOSTOTIC SYNDACTYLY WITH PHALANGEAL REDUCTION, MALIK-PERCIN TYPE to ?Camptosynpolydactyly, complex, OMIM:607539; Syndactyly, mesoaxial synostotic, with phalangeal reduction, OMIM:609432SPLIT HAND AND FOOT MALFORMATION; MESOAXIAL SYNOSTOTIC SYNDACTYLY WITH PHALANGEAL REDUCTION, MALIK-PERCIN TYPE
Fetal anomalies v1.713 CNTN1 Arina Puzriakova gene: CNTN1 was added
gene: CNTN1 was added to Fetal anomalies. Sources: Expert list,Radboud University Medical Center, Nijmegen,Expert Review Amber
Mode of inheritance for gene: CNTN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNTN1 were set to 19026398; 32779773
Phenotypes for gene: CNTN1 were set to Myopathy, congenital, Compton-North, OMIM:612540
Penetrance for gene: CNTN1 were set to Complete
Fetal anomalies v1.674 SMARCC1 Arina Puzriakova commented on gene: SMARCC1: Penetrance for gene SMARCC1 was set from None to Incomplete
Fetal anomalies v1.670 SPTBN5 Arina Puzriakova gene: SPTBN5 was added
gene: SPTBN5 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SPTBN5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPTBN5 were set to 32732226
Phenotypes for gene: SPTBN5 were set to Multicystic kidney; Oligohydramnios
Review for gene: SPTBN5 was set to RED
Added comment: Novel candidate gene identified in a fetus with multicystic kidney and oligohydramnios detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hygroma coli, spina bifida, polycystic kidneys, facial dysmorphism, common mesenterin, rachischisis, sacral vertebral agenesis. Compound heterozygous variants including a truncating variant were found by exome sequencing.
Sources: Literature
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 v1.667 DNAH2 Arina Puzriakova changed review comment from: Novel candidate gene identified in a fetus with hydrops and complex cardiopathy detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hydrops, heterotaxy, complex cardiopathy, hypotrophic splenium, and common mesentery. Compound heterozygous variants including a truncating variant were found exome sequencing.
Sources: Literature; to: Novel candidate gene identified in a fetus with hydrops and complex cardiopathy detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hydrops, heterotaxy, complex cardiopathy, hypotrophic splenium, and common mesentery. Compound heterozygous variants including a truncating variant were found by exome sequencing.
Sources: Literature
Fetal anomalies v1.667 DNAH2 Arina Puzriakova gene: DNAH2 was added
gene: DNAH2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: DNAH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH2 were set to 32732226
Phenotypes for gene: DNAH2 were set to Hydrops; Complex cardiopathy
Review for gene: DNAH2 was set to RED
Added comment: Novel candidate gene identified in a fetus with hydrops and complex cardiopathy detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hydrops, heterotaxy, complex cardiopathy, hypotrophic splenium, and common mesentery. Compound heterozygous variants including a truncating variant were found exome sequencing.
Sources: Literature
Fetal anomalies v1.660 RFWD3 Arina Puzriakova Phenotypes for gene: RFWD3 were changed from Fanconi anaemia to ?Fanconi anemia, complementation group W, OMIM:617784
Fetal anomalies v1.630 KIDINS220 Eleanor Williams changed review comment from: Associated with Spastic paraplegia, intellectual disability, nystagmus, and obesity #617296 in OMIM for monoallelic cases.

2 biallelic cases associated with cerebral ventriculomegaly and limb contractures, plus a mouse model that shows some phenotypic overlap:

PMID: 33205811 - Jacquemin et al 2021 - report a consanguineous family of Pakistani origin in which 3 fetuses presented with brain ventriculomegaly and limb contractures. Autopsy of one fetus identifed bilateral club feet and club hands. They were found by WES to share a very rare homozygous variant of KIDINS220 (c.2327_2336del, Gln713_Leu715del). Parents and healthy siblings were heterozygous for this variant. Severe ventriculomegaly was diagnosed as early as 14 weeks. Binding of KIDINS220 to TrkA is decreased by the deletion mutation.

PMID: 28934391 - Mero et al 2017 - report a consanguineous couple in which 4 fetuses presented with enlarged cerebral ventricles and limb contractures. Exome sequencing in two of the fetuses found a shared homozygous frameshift variant in exon 24 in KIDINS220 ((NM_020738:c.3394_3403del; p.Gln1132Serfs*30). Healthy family members were either carriers or homozygous for the wild-type allele. It is thought that the variant leads to NMD and complete loss of KIDINS220 protein.

PMID: 28934391 - Cesca et al 2011 - report a Kidins220 mutant mouse. Kidins220 -/- mice die at late stages of gestation and show extensive neuronal cell death in the central and peripheral nervous systems, as well as heart malformations.; to: Associated with Spastic paraplegia, intellectual disability, nystagmus, and obesity #617296 in OMIM for monoallelic cases.

2 biallelic cases associated with cerebral ventriculomegaly and limb contractures, plus a mouse model that shows some phenotypic overlap:

PMID: 33205811 - Jacquemin et al 2021 - report a consanguineous family of Pakistani origin in which 3 fetuses presented with brain ventriculomegaly and limb contractures. Autopsy of one fetus identifed bilateral club feet and club hands. They were found by WES to share a very rare homozygous variant of KIDINS220 (c.2327_2336del, Gln713_Leu715del). Parents and healthy siblings were heterozygous for this variant. Severe ventriculomegaly was diagnosed as early as 14 weeks. Binding of KIDINS220 to TrkA is decreased by the deletion mutation.

PMID: 28934391 - Mero et al 2017 - report a consanguineous couple in which 4 fetuses presented with enlarged cerebral ventricles and limb contractures. Exome sequencing in two of the fetuses found a shared homozygous frameshift variant in exon 24 in KIDINS220 ((NM_020738:c.3394_3403del; p.Gln1132Serfs*30). Healthy family members were either carriers or homozygous for the wild-type allele. It is thought that the variant leads to NMD and complete loss of KIDINS220 protein.

PMID: 22048169 - Cesca et al 2011 - report a Kidins220 mutant mouse. Kidins220 -/- mice die at late stages of gestation and show extensive neuronal cell death in the central and peripheral nervous systems, as well as heart malformations.
Fetal anomalies v1.630 KIDINS220 Eleanor Williams changed review comment from: Associated with Spastic paraplegia, intellectual disability, nystagmus, and obesity #617296 in OMIM for monoallelic cases.

2 biallelic cases associated with cerebral ventriculomegaly and limb contractures in the following two publications:

PMID: 33205811 - Jacquemin et al 2021 - report a consanguineous family of Pakistani origin in which 3 fetuses presented with brain ventriculomegaly and limb contractures. Autopsy of one fetus identifed bilateral club feet and club hands. They were found by WES to share a very rare homozygous variant of KIDINS220 (c.2327_2336del, Gln713_Leu715del). Parents and healthy siblings were heterozygous for this variant. Severe ventriculomegaly was diagnosed as early as 14 weeks. Binding of KIDINS220 to TrkA is decreased by the deletion mutation.

PMID: 28934391 - Mero et al 2017 - report a consanguineous couple in which 4 fetuses presented with enlarged cerebral ventricles and limb contractures. Exome sequencing in two of the fetuses found a shared homozygous frameshift variant in exon 24 in KIDINS220 ((NM_020738:c.3394_3403del; p.Gln1132Serfs*30). Healthy family members were either carriers or homozygous for the wild-type allele. It is thought that the variant leads to NMD and complete loss of KIDINS220 protein.

PMID: 28934391 - Cesca et al 2011 - report a Kidins220 mutant mouse. Kidins220 -/- mice die at late stages of gestation and show extensive neuronal cell death in the central and peripheral nervous systems, as well as heart malformations.; to: Associated with Spastic paraplegia, intellectual disability, nystagmus, and obesity #617296 in OMIM for monoallelic cases.

2 biallelic cases associated with cerebral ventriculomegaly and limb contractures, plus a mouse model that shows some phenotypic overlap:

PMID: 33205811 - Jacquemin et al 2021 - report a consanguineous family of Pakistani origin in which 3 fetuses presented with brain ventriculomegaly and limb contractures. Autopsy of one fetus identifed bilateral club feet and club hands. They were found by WES to share a very rare homozygous variant of KIDINS220 (c.2327_2336del, Gln713_Leu715del). Parents and healthy siblings were heterozygous for this variant. Severe ventriculomegaly was diagnosed as early as 14 weeks. Binding of KIDINS220 to TrkA is decreased by the deletion mutation.

PMID: 28934391 - Mero et al 2017 - report a consanguineous couple in which 4 fetuses presented with enlarged cerebral ventricles and limb contractures. Exome sequencing in two of the fetuses found a shared homozygous frameshift variant in exon 24 in KIDINS220 ((NM_020738:c.3394_3403del; p.Gln1132Serfs*30). Healthy family members were either carriers or homozygous for the wild-type allele. It is thought that the variant leads to NMD and complete loss of KIDINS220 protein.

PMID: 28934391 - Cesca et al 2011 - report a Kidins220 mutant mouse. Kidins220 -/- mice die at late stages of gestation and show extensive neuronal cell death in the central and peripheral nervous systems, as well as heart malformations.
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 v1.438 KIF5C Arina Puzriakova Phenotypes for gene: KIF5C were changed from CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 2 to Cortical dysplasia, complex, with other brain malformations 2, OMIM:615282; Complex cortical dysplasia with other brain malformations 2, MONDO:0014116
Fetal anomalies v1.433 KIF2A Arina Puzriakova Phenotypes for gene: KIF2A were changed from MALFORMATIONS OF CORTICAL DEVELOPMENT AND MICROCEPHALY. to Cortical dysplasia, complex, with other brain malformations 3, OMIM:615411; Complex cortical dysplasia with other brain malformations 3, MONDO:0014170
Fetal anomalies v1.387 FANCL Arina Puzriakova Phenotypes for gene: FANCL were changed from FANCL-RELATED FANCONI ANEMIA; FANCONI ANEMIA to Fanconi anemia, complementation group L, OMIM:614083; Fanconi anemia complementation group L, MONDO:0013566
Fetal anomalies v1.272 MYH7 Arina Puzriakova Phenotypes for gene: MYH7 were changed from Cardiomyopathy, dilated, 1S; Cardiomyopathy, hypertrophic, 1; Laing distal myopathy; Left ventricular noncompaction 5 to Laing distal myopathy, OMIM:160500; Laing early-onset distal myopathy, MONDO:0008050; Cardiomyopathy, hypertrophic, 1, OMIM:192600; Hypertrophic cardiomyopathy 1, MONDO:0008647; Cardiomyopathy, dilated, 1S, OMIM:613426; Dilated cardiomyopathy 1S, MONDO:0013262; Left ventricular noncompaction 5, OMIM:613426
Fetal anomalies v1.246 MACF1 Arina Puzriakova Phenotypes for gene: MACF1 were changed from Lissencephaly 9 with complex brainstem malformation to Lissencephaly 9 with complex brainstem malformation, OMIM:618325; Lissencephaly 9 with complex brainstem malformation, MONDO:0032677
Fetal anomalies v1.215 FANCL Rhiannon Mellis reviewed gene: FANCL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anemia, complementation group L; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.214 IDH1 Rhiannon Mellis gene: IDH1 was added
gene: IDH1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: IDH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: IDH1 were set to 22025298; 22057236; 22057234; 24049096
Phenotypes for gene: IDH1 were set to Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria 614875; Maffucci syndrome 614569; Ollier disease/ Dyschondroplasia 166000
Review for gene: IDH1 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

Copied from skeletal dysplasias panel: Lysosomal storage diseases with skeletal involvement (dysostosis multiplex gp of SD), disorganized development of skeletal components gp of SD - Somatic mosaicism seen in at least 3 cases with enchondromatosis (various types)/ metaphyseal chondromatosis. amber/green -Somatic mosaic missense variants in enchondromas. Listed in Bonafe (MetaphysealchondromatosiswithD-2-hydroxyglutaric aciduria).
Sources: Expert list
Fetal anomalies v1.214 KIF2A Rhiannon Mellis reviewed gene: KIF2A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cortical dysplasia, complex, with other brain malformations 3; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.214 KIF5C Rhiannon Mellis reviewed gene: KIF5C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cortical dysplasia, complex, with other brain malformations 2; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.214 MACF1 Rhiannon Mellis gene: MACF1 was added
gene: MACF1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MACF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: MACF1 were set to Lissencephaly 9 with complex brainstem malformation
Review for gene: MACF1 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): Cerebellar hypoplasia; Cerebral malformations; Malformations of cortical development
Sources: Expert list
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
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 v1.186 ERCC5 Arina Puzriakova Phenotypes for gene: ERCC5 were changed from XERODERMA PIGMENTOSUM COMPLEMENTATION GROUP G to Cerebrooculofacioskeletal syndrome 3, OMIM:616570; Cerebrooculofacioskeletal syndrome 3, MONDO:0014696
Fetal anomalies v1.185 TUBB3 Rhiannon Mellis reviewed gene: TUBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cortical dysplasia, complex, with other brain malformations 1; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.185 TUBG1 Rhiannon Mellis reviewed gene: TUBG1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cortical dysplasia, complex, with other brain malformations 4; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.185 UBE2T Rhiannon Mellis reviewed gene: UBE2T: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anemia, complementation group T; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
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 v1.155 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)
Fetal anomalies v1.136 TUBB2A Arina Puzriakova Phenotypes for gene: TUBB2A were changed from CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 5 to Cortical dysplasia, complex, with other brain malformations 5, OMIM:615763; Complex cortical dysplasia with other brain malformations 5, MONDO:0014337
Fetal anomalies v1.113 COX6B1 Arina Puzriakova Phenotypes for gene: COX6B1 were changed from MITOCHONDRIAL COMPLEX IV DEFICIENCY to Mitochondrial complex IV deficiency, nuclear type 7, OMIM:619051
Fetal anomalies v1.112 SCO1 Arina Puzriakova Phenotypes for gene: SCO1 were changed from MITOCHONDRIAL COMPLEX IV DEFICIENCY to Mitochondrial complex IV deficiency, nuclear type 4, OMIM:619048
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
Fetal anomalies v1.95 B9D2 Rhiannon Mellis gene: B9D2 was added
gene: B9D2 was added to Fetal anomalies. Sources: Literature,NHS GMS
Mode of inheritance for gene: B9D2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B9D2 were set to PMID: 21763481; 26092869
Phenotypes for gene: B9D2 were set to Joubert syndrome; Meckel syndrome
Review for gene: B9D2 was set to GREEN
gene: B9D2 was marked as current diagnostic
Added comment: 2 fetuses with MKS in one consanguineous family with homozygous B9D2 pathogenic variants. Functional studies of the variant confirmed loss of function. (PMID: 21763481)
2 unrelated patients with Joubert syndrome with different compound het B9D2 variants. (PMID: 26092869)

NB: Currently Green in ciliopathies panels. We report variants in this gene on our postnatal ciliopathies panel at GOSH/NTGLH.
Sources: Literature, NHS GMS
Fetal anomalies v1.95 KIF14 Rhiannon Mellis gene: KIF14 was added
gene: KIF14 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: KIF14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF14 were set to PMID: 24128419; 30388224; 28892560; 29343805
Phenotypes for gene: KIF14 were set to ?Meckel syndrome 12; Microcephaly 20, primary
Review for gene: KIF14 was set to GREEN
gene: KIF14 was marked as current diagnostic
Added comment: Two fetuses in one family with complex multiple congenital anomalies consistent with ciliopathy phenotype. (PMID: 24128419)
Four more families with fetuses with similar phenotype (microcephaly, brain malformations and renal agenesis or hypodysplasia). Also functional (zebrafish) studies. Authors conclude that LOF variants cause the above syndromic phenotype while hypomorphic variants cause microcephaly without kidney defects. (PMID: 30388224)

Four unrelated families with AR primary microcephaly and biallelic KIF14 pathogenic variants (PMID: 28892560)
Four more unrelated families with AR primary microcephaly and biallelic KIF14 pathogenic variants. Two sibs from one of the families were fetuses with severe microcephaly detected prenatally and leading to termination of pregnancy. (PMID: 29343805)
Sources: Literature
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
Fetal anomalies v1.94 TOGARAM1 Arina Puzriakova gene: TOGARAM1 was added
gene: TOGARAM1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TOGARAM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOGARAM1 were set to 32747439
Phenotypes for gene: TOGARAM1 were set to Cleft of the lip and palate; Microphthalmia; Cerebral dysgenesis; Hydrocephalus
Added comment: PMID: 32747439 (2020) - Novel gene-disease association. In two sibling fetuses with a malformation disorder characterised by microcephaly, severe cleft lip and palate, microphthalmia, and brain anomalies, WES revealed compound heterozygous variants ([c.1102C>T, p.Arg368Trp] and [c.3619C>T, p.Arg1207*]) in the TOGARAM1 gene.

Functional analysis of the missense variant in a C. elegans model showed impaired lipophilic dye uptake, with shorter and altered cilia in sensory neurons. In vitro analysis revealed faster microtubule polymerisation compared to wild-type, suggesting aberrant tubulin binding.
Sources: Literature
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 COL3A1 Rhiannon Mellis gene: COL3A1 was added
gene: COL3A1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: COL3A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: COL3A1 were set to PMID: 28258187; 28742248; 25205403; 27168972; 24922459
Phenotypes for gene: COL3A1 were set to HP:0002126; HP:0001883; HP:0006496
Penetrance for gene: COL3A1 were set to Incomplete
Review for gene: COL3A1 was set to GREEN
Added comment: On OMIM COL3A1 has a polymicrogyria phenotype in the biallelic form, as well as talipes and other features (PMID: 28258187; PMID: 28742248; PMID: 25205403). No specifically prenatal reports of polymicrogyria in the literature but this feature would be detectable on fetal US and especially on fetal MRI.

A monoallelic COL3A1 variant has been reported in one case in a prenatal exome series (PMID: 27168972), causing EDS IV with a prenatal phenotype of forearm hypoplasia and phalangeal defects. PMID: 24922459 evidences that limb hypoplasia/limb reduction is observed in a small subset of EDS IV patients (5 unrelated cases), as well as talipes in a larger number, and occasionally facial clefts – all of which would be prenatally detectable features.
Sources: Literature
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 v1.72 ITGA8 Rebecca Foulger changed review comment from: PMID:24439109, Humbert et al. (2014). In 3 fetuses of Roma Gypsy descent with bilateral renal hypodysplasia/aplasia-1, Humbert et al identified a homozygous T-to-C transition in intron 27 of the ITGA8 gene (c.2982+2T-C) leading to the skipping of exon 28 and an in-frame 34 amino acide deletion. 1 unaffected mother was heterozygous for the variant. All fetuses had bilateral renal agenesis and anhydramnios, resulting in death in utero.

The authors also identified 2 siblings from West African with bilateral renal hypodysplasia/aplasia-1 and compound het variants in ITGA8 (Glu541AlafsTer12 and G407R). The missense variant was found once in the Exome Variant Server (1 in 13,005). One of the siblings was a fetus that aborted at gestational week 24 due to bilateral renal agenesis and anhydramnios. The second sibling died in the perinatal period.; to: PMID:24439109, Humbert et al. (2014). In 3 fetuses of Roma Gypsy descent with bilateral renal hypodysplasia/aplasia-1, Humbert et al identified a homozygous T-to-C transition in intron 27 of the ITGA8 gene (c.2982+2T-C) leading to the skipping of exon 28 and an in-frame 34 amino acide deletion. 1 unaffected mother was heterozygous for the variant. All fetuses had bilateral renal agenesis and anhydramnios, resulting in death in utero.

The authors also identified 2 siblings from West African with bilateral renal hypodysplasia/aplasia-1 and compound het variants in ITGA8 (Glu541AlafsTer12 and G407R). The missense variant was found once in the Exome Variant Server (1 in 13,005). One of the siblings was a fetus that aborted at gestational week 24 due to bilateral renal agenesis and anhydramnios. The second sibling died in the perinatal period and presented with BRA and bilateral cryptorchidism.
Fetal anomalies v1.71 ITGA8 Rebecca Foulger changed review comment from: PMID:24439109, Humbert et al. (2014). In 3 fetuses of Roma Gypsy descent with bilateral renal hypodysplasia/aplasia-1, Humbert et al identified a homozygous T-to-C transition in intron 27 of the ITGA8 gene (c.2982+2T-C) leading to the skipping of exon 28 and an in-frame 34 amino acide deletion. 1 unaffected mother was heterozygous for the varinat. All fetuses had bilateral renal agenesis and anhydramnios, resulting in death in utero.

The authors also identified 2 siblings from West African with bilateral renal hypodysplasia/aplasia-1 and compound het variants in ITGA8 (Glu541AlafsTer12 and G407R). The missense variant was found once in the Exome Variant Server (1 in 13,005). One of the siblings was a fetus that aborted at gestational week 24 due to bilateral renal agenesis and anhydramnios. The second sibling died in the perinatal period.; to: PMID:24439109, Humbert et al. (2014). In 3 fetuses of Roma Gypsy descent with bilateral renal hypodysplasia/aplasia-1, Humbert et al identified a homozygous T-to-C transition in intron 27 of the ITGA8 gene (c.2982+2T-C) leading to the skipping of exon 28 and an in-frame 34 amino acide deletion. 1 unaffected mother was heterozygous for the variant. All fetuses had bilateral renal agenesis and anhydramnios, resulting in death in utero.

The authors also identified 2 siblings from West African with bilateral renal hypodysplasia/aplasia-1 and compound het variants in ITGA8 (Glu541AlafsTer12 and G407R). The missense variant was found once in the Exome Variant Server (1 in 13,005). One of the siblings was a fetus that aborted at gestational week 24 due to bilateral renal agenesis and anhydramnios. The second sibling died in the perinatal period.
Fetal anomalies v1.69 ITGA8 Rebecca Foulger commented on gene: ITGA8: PMID:24439109, Humbert et al. (2014). In 3 fetuses of Roma Gypsy descent with bilateral renal hypodysplasia/aplasia-1, Humbert et al identified a homozygous T-to-C transition in intron 27 of the ITGA8 gene (c.2982+2T-C) leading to the skipping of exon 28 and an in-frame 34 amino acide deletion. 1 unaffected mother was heterozygous for the varinat. All fetuses had bilateral renal agenesis and anhydramnios, resulting in death in utero.

The authors also identified 2 siblings from West African with bilateral renal hypodysplasia/aplasia-1 and compound het variants in ITGA8 (Glu541AlafsTer12 and G407R). The missense variant was found once in the Exome Variant Server (1 in 13,005). One of the siblings was a fetus that aborted at gestational week 24 due to bilateral renal agenesis and anhydramnios. The second sibling died in the perinatal period.
Fetal anomalies v1.68 REN Rebecca Foulger commented on gene: REN: PMID:31736371. He et al., performed a study to identify the potentially pathogenic gene variants that contribute to the AR renal tubular dysgenesis (RTD) in an aborted fetus. WES was performed on the fetus and his parents. Compound heterozygous variants (c.963T>A, p.Y321X and c.492+1G>A splicing site mutation) were identified in the fetus, one inherited from each parent.
Fetal anomalies v1.54 PSAT1 Rebecca Foulger commented on gene: PSAT1: PMID:31903955 (Ni et al., 2019) report Chinese Neu-Laxova syndrome (NLS) patients from 2 families. Compound het PSAT1 variants R342W and Y70N were found in the proband from family 1. (PHGDH variants were identified in family 2).
Fetal anomalies v1.44 AHCY Rebecca Foulger commented on gene: AHCY: PMID:20852937. Grubbs et al., 2010 report 2 sisters born with fetal hydrops and compound het for 2 variants in AHCY (p.Arg49Cys and p.Asp86Gly). Phenotypes included severe hypotonia/myopathy, feeding problems, and respiratory failure. The sisters died age 25 days and 122 days.
Fetal anomalies v1.40 TUBA8 Rebecca Foulger Phenotypes for gene: TUBA8 were changed from POLYMICROGYRIA WITH OPTIC NERVE HYPOPLASIA to POLYMICROGYRIA WITH OPTIC NERVE HYPOPLASIA; Cortical dysplasia, complex, with other brain malformations 8, 613180
Fetal anomalies v1.14 MYH11 Rebecca Foulger Added comment: Comment on mode of inheritance: Set mode of inheritance to BIALLELIC to match papers: compound het and homozygous MYH11 variants associated with MMIH.
Fetal anomalies v1.3 TUBA8 Zornitza Stark reviewed gene: TUBA8: Rating: RED; Mode of pathogenicity: None; Publications: 19896110, 31481326, 28388629; Phenotypes: Cortical dysplasia, complex, with other brain malformations 8, MIM# 613180; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
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 v0.359 KLF1 Rebecca Foulger Added comment: Comment on mode of inheritance: Updated MOI from 'Monoallelic' to 'BOTH AD+AR' (after agreement from Rhiannon Mellis, GOSH), to match the MOI on the Fetal hydrops v.1.16 panel. The expanded MOI is based on compound heterozygous cases in PMID:25724378 and PMID:28361594.
Fetal anomalies v0.352 SCO2 Rebecca Foulger commented on gene: SCO2: PMID:18924171 (Verdijk et al, 2008) report the first prenatal diagnosis of a compound heterozygous SCO2 variant in the literature. The sibling died of fatal infantile cardioencephalomyopathy.
Fetal anomalies v0.341 NMNAT2 Michael Coleman gene: NMNAT2 was added
gene: NMNAT2 was added to Fetal anomalies. Sources: Research
Mode of inheritance for gene: NMNAT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NMNAT2 were set to PMID: 31136762
Phenotypes for gene: NMNAT2 were set to hydrops fetalis; cystic hygroma; bilateral hypoplastic lungs; hydrocephalus; hypoplastic cerebellum; severely reduced skeletal muscle mass or absence; flexion contractures of all extremities; micrognathia; cleft palate; hydropic placenta
Penetrance for gene: NMNAT2 were set to Complete
Review for gene: NMNAT2 was set to GREEN
Added comment: Closely related phenotype in homozygous null mouse (PMID 23946398)
Sources: Research
Fetal anomalies v0.316 INTU Rebecca Foulger Added comment: Comment on mode of inheritance: Biallelic inheritance matches AR/compound het variant identified in Normand et al., 2018 (PMID:30266093) and MIM:617925/617926.
Fetal anomalies v0.314 EIF2B2 Rebecca Foulger Added comment: Comment on mode of inheritance: Biallelic inheritance matches AR/compound het variant identified in Normand et al., 2018 (PMID:30266093) and MIM:2603896.
Fetal anomalies v0.313 DOK7 Rebecca Foulger Added comment: Comment on mode of inheritance: Biallelic inheritance matches AR/compound het variant identified in Normand et al., 2018 (PMID:30266093) and MIM:254300.
Fetal anomalies v0.312 NDUFAF5 Rebecca Foulger Added comment: Comment on mode of inheritance: Biallelic inheritance matches AR/compound het variant identified in Normand et al., 2018 (PMID:30266093) and MIM:618238.
Fetal anomalies v0.311 ABCD4 Rebecca Foulger commented on gene: ABCD4: 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: Rate as Green all genes associated with cobalamin metabolism which have a perinatal phenotype listed in PMID:20301503 (Table 4). Although ABCD4 (CblJ complementation group) is associated with congenital heart disease in PMID:20301503, the Disease confidence rating in Gene2Phenotype is 'probable' with two compound het cases listed in OMIM. Therefore kept rating as Amber awaiting further evidence.
Fetal anomalies v0.311 TCF20 Rebecca Foulger edited their review of gene: TCF20: Added comment: As agreed with Anna de Burca (Genomics England Clinical team): Keep TCF20 as Amber: the structural phenotypes are variable (and largely mild). All individuals have ID/DD but the accompanying dysmorphic features are inconsistent, and the authors suggest additional genes may be responsible/modifying- some of the patients had variants in additional genes (or the phenotypes might be very very rare).; Changed publications: 30739909, 30819258
Fetal anomalies v0.310 NDUFAF5 Rebecca Foulger gene: NDUFAF5 was added
gene: NDUFAF5 was added to Fetal anomalies. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NDUFAF5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFAF5 were set to 18940309; 30266093; 21620786
Phenotypes for gene: NDUFAF5 were set to Mitochondrial complex I deficiency, nuclear type 16, 618238
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 v0.293 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 v0.276 PKD1 Rebecca Foulger commented on gene: PKD1: PMID:20558538 (Vujic et al., 2010) was added as a publication by Julia Baptista. The authors describe two pedigrees each with two patients with onset of polycystic kidney disease in-utero. Mutation analysis suggested that both families inherited, in trans, two incompletely penetrant PKD1 alleles, thus supporting autosomal recessive PKD.
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
Fetal anomalies v0.273 MRPS22 Rebecca Foulger edited their review of gene: MRPS22: Added comment: 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 compound heterozygous variants in MRPS22 in a case where the main ultrasound finding was Hydrops, CNS malformations, cardiomyopathy (Table 1).; Changed phenotypes: Hydrops, CNS malformations, cardiomyopathy
Fetal anomalies v0.247 CNOT1 Rebecca Foulger commented on gene: CNOT1: Kruszka et al., 2019 (PMID:31006510) report two unrelated individuals with semilobar holoprosencephaly who have the identical de novo missense variant in the gene CNOT1. (c.1603C>T [p.Arg535Cys]). Proband 1 was born after a pregnancy complicated by IUGR. Additional medical problems include diabetes, pancreatice exocrine insufficiency and facial characteristics. No diabetic or pancreatic phenotype was recorded for proband 2.
Fetal anomalies v0.216 TBL1XR1 Rebecca Foulger commented on gene: TBL1XR1: Evidence assessment for 'Pierpont syndrome, 602342' comprises 6 unrelated patients from Heinen et al. 2016 (PMID:26769062) with the same de novo heterozygous missense variant in the TBL1XR1 gene (c.1337A>G, p.Y446C). Plus a male child with the same missense variant from Kahlert et al., 2017 (PMID:28562391).
Fetal anomalies v0.210 POMK Rebecca Foulger commented on gene: POMK: Patient 3 in PMID:24925318 (Di Costanzo et al, 2014) was an Italian male presenting with the most severe form of dystroglycanopathy, Walker–Warburg syndrome (WWS) and compound het variants in POMK. Macrocephaly and hydrocephalus were diagnosed in utero upon prenatal ultrasound at 32 weeks of gestation.
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
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
Fetal anomalies v0.197 DSTYK Rebecca Foulger commented on gene: DSTYK: Note that a new gene:disorder association was added to DDG2P in March 2019: Autosomal Recessive Complicated Spastic Paraparesis SPG23. DDG2P Disease confidence: probable. DDG2P mode of pathogenicity/mutation consequence: loss of function. DDG2P mode of inheritance: biallelic. Not yet included the spastic paraplegia phenotype (or biallelic inheritance) on this Fetal anomalies panel for DSTYK because the 3 families identified in PMID:28157540 have the same variant, and haplotype analysis suggests a Founder effect.
Fetal anomalies v0.195 SIM1 Rebecca Foulger commented on gene: SIM1: Added 'multifactorial' tag to represent the 'Mu/Multifactorial' component of the mode of inheritance reported in OMM (AR,AD,Mu).
Fetal anomalies v0.186 FLVCR2 Rebecca Foulger edited their review of gene: FLVCR2: Added comment: Additional evidence from PMID:30712878: Compound heterozygous variants identified in FLVCR2 from fetal exome sequencing in Petrovski et al., 2019 (Whole-exome sequencing in the evaluation of fetal stuctural anomalies: a prospective cohort study, PMID:30712878).; Changed publications: 30712878
Fetal anomalies v0.186 RAPSN Rebecca Foulger edited their review of gene: RAPSN: Added comment: Additional evidence from PMID:30712878: Compound heterozygous variants identified in RAPSN from fetal exome sequencing in Petrovski et al., 2019 (Whole-exome sequencing in the evaluation of fetal stuctural anomalies: a prospective cohort study, PMID:30712878).; Changed publications: 30712878
Fetal anomalies v0.185 WDR19 Rebecca Foulger edited their review of gene: WDR19: Added comment: Additional evidence from PMID:30266093: AR/compound het variant identified in WDR19 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 v0.185 TMEM67 Rebecca Foulger edited their review of gene: TMEM67: Added comment: Additional evidence from PMID:30266093: AR/compound het variant identified in TMEM67 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 v0.185 RYR1 Rebecca Foulger edited their review of gene: RYR1: Added comment: Additional evidence from PMID:30266093: AR/compound het variant identified in RYR1 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 v0.185 LAMC3 Rebecca Foulger edited their review of gene: LAMC3: Added comment: Additional evidence from PMID:30266093: AR/compound het variant identified in LAMC3 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 v0.185 DYNC2H1 Rebecca Foulger edited their review of gene: DYNC2H1: Added comment: Additional evidence from PMID:30266093: AR/compound het variant identified in DYNC2H1 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 v0.185 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 v0.185 C5orf42 Rebecca Foulger edited their review of gene: C5orf42: Added comment: Additional evidence from PMID:30266093: AR/compound het variant identified in C5orf42 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 v0.185 ALG12 Rebecca Foulger edited their review of gene: ALG12: Added comment: Additional evidence from PMID:30266093: AR/compound het variant identified in ALG12 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 v0.183 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 v0.183 RYR1 Rebecca Foulger edited their review of gene: RYR1: Added comment: Additional evidence from PAGE study: Diagnostic Compound heterozygous variants identified in RYR1 from fetalexome sequencing inLord et al., 2019 (PMID:30712880).; Changed publications: 30712880
Fetal anomalies v0.183 PIEZO1 Rebecca Foulger edited their review of gene: PIEZO1: Added comment: Additional evidence from PAGE study: Diagnostic Compound heterozygous variants identified in PIEZO1 from fetalexome sequencing inLord et al., 2019 (PMID:30712880).; Changed publications: 30712880
Fetal anomalies v0.183 DYNC2H1 Rebecca Foulger edited their review of gene: DYNC2H1: Added comment: Additional evidence from PAGE study: Diagnostic Compound heterozygous variants identified in DYNC2H1 from fetalexome sequencing inLord et al., 2019 (PMID:30712880).; Changed publications: 30712880
Fetal anomalies v0.161 SLX4 Rebecca Foulger commented on gene: SLX4: Sufficient unrelated cases in OMIM supporting a link between SLX4 variants and Fanconi anaemia, including a Dutch boy and 3 German siblings from PMID:21240277, and a 15 year old Indian girl and a 22 year old male from PMID:21240275- the compound het variants in the 22 yr old male included a large genomic deletion.
Fetal anomalies v0.135 COMP Rebecca Foulger Source Expert Review Red was added to COMP.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Fetal anomalies v0.134 COMP Rebecca Foulger edited their review of gene: COMP: 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 COMP gene rating from Green to Red. Additional notes from clinical review: Onset is later.; Changed rating: RED
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 v0.110 LDB3 Rebecca Foulger commented on gene: LDB3: Changed rating to Amber to reflect DDG2P Disease confidence of 'DD and IF' for LEFT VENTRICULAR NON-COMPACTION TYPE 3; CARDIOMYOPATHY DILATED TYPE 1C; MYOPATHY MYOFIBRILLAR TYPE 4.
Fetal anomalies v0.110 BRCA2 Rebecca Foulger commented on gene: BRCA2: Changed rating to Amber to reflect DDG2P Disease confidence of 'DD and IF' for FANCONI ANEMIA COMPLEMENTATION GROUP D TYPE 1.
Fetal anomalies v0.95 MITF Rebecca Foulger commented on gene: MITF: In 2 unrelated children with coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness (COMMAD; 617306), whose parents exihibited features of WS2A, George et al. (2016, PMID:27889061) identified compound heterozygosity for variants in the MITF gene.
Fetal anomalies v0.85 EMG1 Rebecca Foulger commented on gene: EMG1: Bowen-Conradi syndrome includes marked prenatal and postnatal growth retardation, microcephaly, a prominent nose with an absent glabellar angle, micrognathia, joint abnormalities including flexion contractures, camptodactyly, rocker-bottom feet, and severe psychomotor delay (PMID:19463982). So far, one EMG1 variant (D86G) recorded for Bowen-Conradi Syndrome, with virtually all affected babies born into Hutterite families. PMID:19463982 does however report that there are at least 4 published (Russian, German, Turkish and two Indian babies) and four unpublished reports of non-Hutterite babies with BCS-compatible features.
Fetal anomalies v0.66 CFC1 Rebecca Foulger commented on gene: CFC1: Further information on evidence for Green rating: Reviewed as Green on the 'Familial non syndromic congenital heart disease' panel in relation to heterotaxy phenotype. 3 cases in OMIM cases to support causation of 'Heterotaxy, visceral, 2, autosomal, 605376' although incomplete penetrance (with phenotypically-normal parent carrying the variant) seen in two cases.
Fetal anomalies v0.63 USP18 Rebecca Foulger edited their review of gene: USP18: Added comment: Rated as 'Probable' in original PAGE list. Rated green on 'Intracerebral calcification disorders' panel and phenotype (pseudo-TORCH syndrome) is appropriate for Fetal panel, as noted by Helen Brittain and Anna de Burca (Genomics England Clinical team). However, kept rating as Amber for now based on insufficient evidence to support causation: One publication (Meuwissen et al. 2016, PMID:27325888) with two families (Turkish and German) with pseudo-TORCH syndrome-2 and homozygous or compound het variants in USP18. Segregation shown in 5 affected individuals plus an unaffected sibling. Cells from patients in both families showed complete absence of the USP18 protein.; Changed publications: 27325888; Changed phenotypes: Pseudo-TORCH syndrome 2, 617397
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 v0.63 TAPT1 Rebecca Foulger edited their review of gene: TAPT1: Added comment: Rated as 'Probable' in original PAGE list. Rated Green on the Osteogenesis imperfecta V1.14 panel, and phenotype (COMPLEX LETHAL OSTEOCHONDRODYSPLASIA) is appropriate for Fetal panel, as noted by Helen Brittain and Anna de Burca (Genomics England Clinical team). However, kept rating as Amber for now based on insufficient evidence to support causation: 2 families (Moroccan and Syrian) reported in OMIM with no further cases identified from the literature.; Changed publications: 26365339; Changed phenotypes: Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type, 616897
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 v0.40 ERCC4 Rebecca Foulger Phenotypes for gene: ERCC4 were changed from XFE PROGEROID SYNDROME; FANCONI ANEMIA, COMPLEMENTATION GROUP Q; PRIMORDIAL DWARFISM; XERODERMA PIGMENTOSUM, GROUP F to XFE PROGEROID SYNDROME; FANCONI ANEMIA, COMPLEMENTATION GROUP Q; PRIMORDIAL DWARFISM; XERODERMA PIGMENTOSUM, GROUP F; Xeroderma pigmentosum, group F, 278760
Fetal anomalies v0.38 TCTN1 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green following email correspondance from Anna de Burca. Originally assigned an Amber rating because of different PAGE/DDG2P ratings for different disorders. Anna notes that TCTN1 is Green on the 'Rare multisystem ciliopathy disorders' panel with Joubert syndrome phenotype, and therefore Green rating is appropriate for this Fetal anomalies panel. 3 cases from the literature to support Green rating: Two Bangladeshi sisters in PMID:21725307 with homozgyous variant in TCTN1. A compound het variant from PMID:26477546 in a male fetus, and PMID:26489806 report an additional compound het case.
Fetal anomalies v0.25 PIEZO1 Rebecca Foulger Added comment: Comment on mode of inheritance: 'BOTH monoallelic and biallelic' MOI is recorded for PIEZO1 on the 'Fetal hydrops' panel. Althought the DDG2P MOI is 'biallelic' for Congenital lymphatic dysplasia with hydrops and/or lymphoedema, the monoallelic MOI comes from the additional gene list compiled by PAGE.
Fetal anomalies v0.9 UQCRQ Rebecca Foulger commented on gene: UQCRQ: DDG2P rating in original PAGE list: Probable for MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX III DEFICIENCY, UQCRQ RELATED
Fetal anomalies v0.9 TUBB3 Rebecca Foulger commented on gene: TUBB3: DDG2P rating in original PAGE list: Probable for CONGENITAL FIBROSIS OF THE EXTRAOCULAR MUSCLES and Probable for CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 1.
Fetal anomalies v0.9 TUBB2A Rebecca Foulger commented on gene: TUBB2A: DDG2P rating in original PAGE list: Confirmed for CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 5
Fetal anomalies v0.9 TUBB Rebecca Foulger commented on gene: TUBB: DDG2P rating in original PAGE list: Confirmed for CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 6 and Confirmed for Circumferential Skin Creases Kunze Type.
Fetal anomalies v0.9 STAT1 Rebecca Foulger commented on gene: STAT1: DDG2P rating in original PAGE list: Confirmed for STAT1 DEFICIENCY COMPLETE, Confirmed for MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASE and Confirmed for FAMILIAL CANDIDIASIS TYPE 7.
Fetal anomalies v0.9 SDHAF1 Rebecca Foulger commented on gene: SDHAF1: DDG2P rating in original PAGE list: Confirmed for MITOCHONDRIAL COMPLEX II DEFICIENCY
Fetal anomalies v0.9 RMND1 Rebecca Foulger commented on gene: RMND1: DDG2P rating in original PAGE list: Probable for ENCEPHALOPATHY ASSOCIATED WITH MULTIPLE OXIDATIVE PHOSPHORYLATION COMPLEX DEFICIENCIES AND A MITOCHONDRIAL TRANSLATION DEFECT
Fetal anomalies v0.9 RAD51C Rebecca Foulger commented on gene: RAD51C: DDG2P rating in original PAGE list: Probable for FANCONI ANEMIA, COMPLEMENTATION GROUP 0
Fetal anomalies v0.9 NDUFV1 Rebecca Foulger commented on gene: NDUFV1: DDG2P rating in original PAGE list: Confirmed for MITOCHONDRIAL COMPLEX I DEFICIENCY
Fetal anomalies v0.9 NDUFS8 Rebecca Foulger commented on gene: NDUFS8: DDG2P rating in original PAGE list: Confirmed for MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY
Fetal anomalies v0.9 NDUFS1 Rebecca Foulger commented on gene: NDUFS1: DDG2P rating in original PAGE list: Confirmed for LEIGH SYNDROME and Confirmed for MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY.
Fetal anomalies v0.9 KIF5C Rebecca Foulger commented on gene: KIF5C: DDG2P rating in original PAGE list: Probable for CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 2
Fetal anomalies v0.9 ERF Rebecca Foulger commented on gene: ERF: DDG2P rating in original PAGE list: Confirmed for COMPLEX CRANIOSYNOSTOSIS and Confirmed for Chitayat syndrome: hyperphalangism, characteristic facies, hallux valgus and bronchomalacia.
Fetal anomalies v0.9 CYC1 Rebecca Foulger commented on gene: CYC1: DDG2P rating in original PAGE list: Confirmed for MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 6
Fetal anomalies v0.9 COX10 Rebecca Foulger commented on gene: COX10: DDG2P rating in original PAGE list: Confirmed for LEIGH SYNDROME and Confirmed for MITOCHONDRIAL COMPLEX IV DEFICIENCY.
Fetal anomalies v0.9 COMP Rebecca Foulger commented on gene: COMP: DDG2P rating in original PAGE list: Confirmed for ARE THE CAUSE OF PSEUDOACHONDROPLASIA and Confirmed for MULTIPLE EPIPHYSEAL DYSPLASIA TYPE 1.
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 v0.7 LDB3 Rebecca Foulger commented on gene: LDB3: Rating in original PAGE file: 'both DD and IF' for LEFT VENTRICULAR NON-COMPACTION TYPE 3 and CARDIOMYOPATHY DILATED TYPE 1C and MYOPATHY MYOFIBRILLAR TYPE 4.
Fetal anomalies v0.3 COMP Rebecca Foulger reviewed gene: COMP: Rating: AMBER; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.1 UQCRQ Rebecca Foulger gene: UQCRQ was added
gene: UQCRQ was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: UQCRQ was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UQCRQ were set to MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX III DEFICIENCY, UQCRQ RELATED
Fetal anomalies v0.1 UQCRB Rebecca Foulger gene: UQCRB was added
gene: UQCRB was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: UQCRB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UQCRB were set to MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX III DEFICIENCY, UQCRB-RELATED
Fetal anomalies v0.1 UBE2T Rebecca Foulger gene: UBE2T was added
gene: UBE2T was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: UBE2T was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UBE2T were set to FANCONI ANEMIA, COMPLEMENTATION GROUP T
Fetal anomalies v0.1 TUBB3 Rebecca Foulger Added phenotypes CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 1 for gene: TUBB3
Fetal anomalies v0.1 TUBB2A Rebecca Foulger gene: TUBB2A was added
gene: TUBB2A was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: TUBB2A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TUBB2A were set to CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 5
Fetal anomalies v0.1 TUBB Rebecca Foulger gene: TUBB was added
gene: TUBB was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: TUBB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TUBB were set to CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 6
Fetal anomalies v0.1 TTC19 Rebecca Foulger gene: TTC19 was added
gene: TTC19 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: TTC19 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTC19 were set to MITOCHONDRIAL COMPLEX III DEFICIENCY
Fetal anomalies v0.1 TMEM70 Rebecca Foulger gene: TMEM70 was added
gene: TMEM70 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: TMEM70 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM70 were set to MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 2
Fetal anomalies v0.1 TMEM126B Rebecca Foulger gene: TMEM126B was added
gene: TMEM126B was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: TMEM126B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM126B were set to Muscle Weakness and Isolated Complex I Deficiency
Fetal anomalies v0.1 TAPT1 Rebecca Foulger gene: TAPT1 was added
gene: TAPT1 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: TAPT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TAPT1 were set to COMPLEX LETHAL OSTEOCHONDRODYSPLASIA
Fetal anomalies v0.1 TACO1 Rebecca Foulger gene: TACO1 was added
gene: TACO1 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: TACO1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TACO1 were set to LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX IV DEFICIENCY
Fetal anomalies v0.1 SURF1 Rebecca Foulger Added phenotypes COMPLEX IV DEFICIENCY for gene: SURF1
Fetal anomalies v0.1 STAT1 Rebecca Foulger gene: STAT1 was added
gene: STAT1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: STAT1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: STAT1 were set to STAT1 DEFICIENCY COMPLETE
Fetal anomalies v0.1 SLX4 Rebecca Foulger gene: SLX4 was added
gene: SLX4 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: SLX4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLX4 were set to FANCONI ANEMIA COMPLEMENTATION GROUP P
Fetal anomalies v0.1 SDHAF1 Rebecca Foulger gene: SDHAF1 was added
gene: SDHAF1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: SDHAF1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SDHAF1 were set to MITOCHONDRIAL COMPLEX II DEFICIENCY
Fetal anomalies v0.1 SCO1 Rebecca Foulger gene: SCO1 was added
gene: SCO1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: SCO1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SCO1 were set to MITOCHONDRIAL COMPLEX IV DEFICIENCY
Fetal anomalies v0.1 RSPH3 Rebecca Foulger gene: RSPH3 was added
gene: RSPH3 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: RSPH3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RSPH3 were set to PRIMARY CILIARY DYSKINESIA WITH CENTRAL-COMPLEX DEFECTS
Fetal anomalies v0.1 RSPH1 Rebecca Foulger gene: RSPH1 was added
gene: RSPH1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: RSPH1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RSPH1 were set to PRIMARY CILIARY DYSKINESIA WITH CENTRAL-COMPLEX AND RADIAL-SPOKE DEFECTS
Fetal anomalies v0.1 RMND1 Rebecca Foulger gene: RMND1 was added
gene: RMND1 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: RMND1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RMND1 were set to ENCEPHALOPATHY ASSOCIATED WITH MULTIPLE OXIDATIVE PHOSPHORYLATION COMPLEX DEFICIENCIES AND A MITOCHONDRIAL TRANSLATION DEFECT
Fetal anomalies v0.1 RAD51C Rebecca Foulger gene: RAD51C was added
gene: RAD51C was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: RAD51C was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RAD51C were set to FANCONI ANEMIA, COMPLEMENTATION GROUP 0
Fetal anomalies v0.1 PEX7 Rebecca Foulger Added phenotypes PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 11 for gene: PEX7
Fetal anomalies v0.1 PEX6 Rebecca Foulger Added phenotypes PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 4 for gene: PEX6
Fetal anomalies v0.1 PEX3 Rebecca Foulger gene: PEX3 was added
gene: PEX3 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: PEX3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX3 were set to PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 12
Fetal anomalies v0.1 PEX26 Rebecca Foulger Added phenotypes PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 8 for gene: PEX26
Fetal anomalies v0.1 PEX2 Rebecca Foulger Added phenotypes PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 5 for gene: PEX2
Fetal anomalies v0.1 PEX19 Rebecca Foulger Added phenotypes PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 14 for gene: PEX19
Fetal anomalies v0.1 PEX16 Rebecca Foulger gene: PEX16 was added
gene: PEX16 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: PEX16 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX16 were set to PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 9
Fetal anomalies v0.1 PEX14 Rebecca Foulger Added phenotypes PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP K for gene: PEX14
Fetal anomalies v0.1 PEX13 Rebecca Foulger Added phenotypes PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 13 for gene: PEX13
Fetal anomalies v0.1 PEX12 Rebecca Foulger Added phenotypes PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 3 for gene: PEX12
Fetal anomalies v0.1 PEX10 Rebecca Foulger Added phenotypes PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 7 for gene: PEX10
Fetal anomalies v0.1 PEX1 Rebecca Foulger gene: PEX1 was added
gene: PEX1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: PEX1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX1 were set to PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 1
Fetal anomalies v0.1 PET100 Rebecca Foulger gene: PET100 was added
gene: PET100 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: PET100 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PET100 were set to MITOCHONDRIAL COMPLEX IV DEFICIENCY
Fetal anomalies v0.1 PALB2 Rebecca Foulger gene: PALB2 was added
gene: PALB2 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: PALB2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PALB2 were set to FANCONI ANEMIA, COMPLEMENTATION GROUP N
Fetal anomalies v0.1 NUBPL Rebecca Foulger gene: NUBPL was added
gene: NUBPL was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: NUBPL was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NUBPL were set to MITOCHONDRIAL COMPLEX I DEFICIENCY
Fetal anomalies v0.1 NDUFV1 Rebecca Foulger gene: NDUFV1 was added
gene: NDUFV1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: NDUFV1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFV1 were set to MITOCHONDRIAL COMPLEX I DEFICIENCY
Fetal anomalies v0.1 NDUFS8 Rebecca Foulger gene: NDUFS8 was added
gene: NDUFS8 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: NDUFS8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFS8 were set to MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY
Fetal anomalies v0.1 NDUFS7 Rebecca Foulger gene: NDUFS7 was added
gene: NDUFS7 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: NDUFS7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFS7 were set to MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY
Fetal anomalies v0.1 NDUFS4 Rebecca Foulger gene: NDUFS4 was added
gene: NDUFS4 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: NDUFS4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFS4 were set to MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY
Fetal anomalies v0.1 NDUFS1 Rebecca Foulger Added phenotypes MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY for gene: NDUFS1
Fetal anomalies v0.1 NDUFA1 Rebecca Foulger gene: NDUFA1 was added
gene: NDUFA1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: NDUFA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: NDUFA1 were set to MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY
Fetal anomalies v0.1 MYH8 Rebecca Foulger gene: MYH8 was added
gene: MYH8 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: MYH8 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: MYH8 were set to CARNEY COMPLEX VARIANT
Fetal anomalies v0.1 MBOAT7 Rebecca Foulger gene: MBOAT7 was added
gene: MBOAT7 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: MBOAT7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MBOAT7 were set to Intellectual Disability Accompanied by Epilepsy and Autistic Features
Fetal anomalies v0.1 LRIT3 Rebecca Foulger gene: LRIT3 was added
gene: LRIT3 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: LRIT3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LRIT3 were set to AUTOSOMAL-RECESSIVE COMPLETE CONGENITAL STATIONARY NIGHT BLINDNESS
Fetal anomalies v0.1 LDB3 Rebecca Foulger gene: LDB3 was added
gene: LDB3 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: LDB3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: LDB3 were set to LEFT VENTRICULAR NON-COMPACTION TYPE 3
Fetal anomalies v0.1 KMT2B Rebecca Foulger gene: KMT2B was added
gene: KMT2B was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: KMT2B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: KMT2B were set to Complex early-onset dystonia
Fetal anomalies v0.1 KIF5C Rebecca Foulger gene: KIF5C was added
gene: KIF5C was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: KIF5C was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: KIF5C were set to CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 2
Fetal anomalies v0.1 GNPTG Rebecca Foulger gene: GNPTG was added
gene: GNPTG was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: GNPTG was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GNPTG were set to MUCOLIPIDOSIS TYPE III COMPLEMENTATION GROUP C
Fetal anomalies v0.1 GNPTAB Rebecca Foulger Added phenotypes MUCOLIPIDOSIS TYPE III COMPLEMENTATION GROUP A for gene: GNPTAB
Fetal anomalies v0.1 FOXRED1 Rebecca Foulger gene: FOXRED1 was added
gene: FOXRED1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: FOXRED1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FOXRED1 were set to MITOCHONDRIAL COMPLEX I DEFICIENCY
Fetal anomalies v0.1 FANCG Rebecca Foulger gene: FANCG was added
gene: FANCG was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: FANCG was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FANCG were set to FANCONI ANEMIA, COMPLEMENTATION GROUP G
Fetal anomalies v0.1 FANCF Rebecca Foulger gene: FANCF was added
gene: FANCF was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: FANCF was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FANCF were set to FANCONI ANEMIA, COMPLEMENTATION GROUP F
Fetal anomalies v0.1 FANCE Rebecca Foulger gene: FANCE was added
gene: FANCE was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: FANCE was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FANCE were set to FANCONI ANEMIA, COMPLEMENTATION GROUP E
Fetal anomalies v0.1 FANCD2 Rebecca Foulger gene: FANCD2 was added
gene: FANCD2 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: FANCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FANCD2 were set to FANCONI ANEMIA, COMPLEMENTATION GROUP D2
Fetal anomalies v0.1 FANCC Rebecca Foulger gene: FANCC was added
gene: FANCC was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: FANCC was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FANCC were set to FANCONI ANEMIA, COMPLEMENTATION GROUP C
Fetal anomalies v0.1 FANCA Rebecca Foulger gene: FANCA was added
gene: FANCA was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: FANCA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FANCA were set to FANCONI ANEMIA, COMPLEMENTATION GROUP A
Fetal anomalies v0.1 ERF Rebecca Foulger gene: ERF was added
gene: ERF was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: ERF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ERF were set to COMPLEX CRANIOSYNOSTOSIS
Fetal anomalies v0.1 ERCC5 Rebecca Foulger gene: ERCC5 was added
gene: ERCC5 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: ERCC5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERCC5 were set to XERODERMA PIGMENTOSUM COMPLEMENTATION GROUP G
Fetal anomalies v0.1 ERCC4 Rebecca Foulger gene: ERCC4 was added
gene: ERCC4 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: ERCC4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERCC4 were set to FANCONI ANEMIA, COMPLEMENTATION GROUP Q
Fetal anomalies v0.1 ERCC3 Rebecca Foulger gene: ERCC3 was added
gene: ERCC3 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: ERCC3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERCC3 were set to XERODERMA PIGMENTOSUM COMPLEMENTATION GROUP B
Fetal anomalies v0.1 ERCC2 Rebecca Foulger Added phenotypes XERODERMA PIGMENTOSUM COMPLEMENTATION GROUP D for gene: ERCC2
Fetal anomalies v0.1 ELAC2 Rebecca Foulger gene: ELAC2 was added
gene: ELAC2 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: ELAC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ELAC2 were set to INFANTILE HYPERTROPHIC CARDIOMYOPATHY, LACTIC ACIDOSIS, AND ISOLATED COMPLEX I DEFICIENCY
Fetal anomalies v0.1 DDHD2 Rebecca Foulger gene: DDHD2 was added
gene: DDHD2 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: DDHD2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DDHD2 were set to COMPLEX HEREDITARY SPASTIC PARAPLEGIA
Fetal anomalies v0.1 CYP11A1 Rebecca Foulger gene: CYP11A1 was added
gene: CYP11A1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE Additional Gene List
Mode of inheritance for gene: CYP11A1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CYP11A1 were set to Adrenal insufficiency, congenital, with 46XY sex reversal, partial or complete 613743
Fetal anomalies v0.1 CYC1 Rebecca Foulger gene: CYC1 was added
gene: CYC1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: CYC1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CYC1 were set to MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 6
Fetal anomalies v0.1 COX6B1 Rebecca Foulger gene: COX6B1 was added
gene: COX6B1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: COX6B1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COX6B1 were set to MITOCHONDRIAL COMPLEX IV DEFICIENCY
Fetal anomalies v0.1 COX15 Rebecca Foulger gene: COX15 was added
gene: COX15 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: COX15 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COX15 were set to MITOCHONDRIAL COMPLEX IV DEFICIENCY
Fetal anomalies v0.1 COX10 Rebecca Foulger Added phenotypes MITOCHONDRIAL COMPLEX IV DEFICIENCY for gene: COX10
Fetal anomalies v0.1 COMP Rebecca Foulger Added phenotypes MULTIPLE EPIPHYSEAL DYSPLASIA TYPE 1 for gene: COMP
Fetal anomalies v0.1 COMP Rebecca Foulger gene: COMP was added
gene: COMP was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: COMP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: COMP were set to ARE THE CAUSE OF PSEUDOACHONDROPLASIA
Fetal anomalies v0.1 CARS2 Rebecca Foulger gene: CARS2 was added
gene: CARS2 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: CARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CARS2 were set to Epileptic encephalopathy with complex movement disorder and regression
Fetal anomalies v0.1 BRIP1 Rebecca Foulger gene: BRIP1 was added
gene: BRIP1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: BRIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: BRIP1 were set to FANCONI ANEMIA, COMPLEMENTATION GROUP J
Fetal anomalies v0.1 BRCA2 Rebecca Foulger gene: BRCA2 was added
gene: BRCA2 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: BRCA2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: BRCA2 were set to FANCONI ANEMIA COMPLEMENTATION GROUP D TYPE 1
Fetal anomalies v0.1 APOPT1 Rebecca Foulger gene: APOPT1 was added
gene: APOPT1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: APOPT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: APOPT1 were set to MITOCHONDRIAL COMPLEX IV DEFICIENCY