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| Hereditary Haemorrhagic Telangiectasia v1.0 | GDF2 |
Bryony Thompson edited their review of gene: GDF2: Added comment: 4 probands/families with heterozygous variants with features of HHT and supporting in vitro or patient cell assays. 2 probands - PMID: 23972370 - first publication of the HHT gene-disease association describing 3 probands with 3 different missense variants & supporting in vitro functional assays. 1 of the missense variants is present in gnomAD v2.1 at a frequency not expected for the disease (p.Arg333Trp, 115 hets; p.Arg68Leu, 0 hets; p.Pro85Leu, 2 hets) 0 probands - PMID: 27081547 - a suspected HHT case with missense p.Arg317Gln, which is present in 11 hets in gnomAD v2.1 0 probands - PMID: 32573726 - identified 4 GDF2 variants (3 missense and 1 synonymous splice site adjacent without strong splice predictions) in a cohort of HHT cases, 3 had likely pathogenic/pathogenic ENG variants that could explain the phenotype, including a case with GDF2 p.Arg333Trp which was reported as pathogenic in the original publication from 2013 0 probands - PMID: 32992168 - a case with PAVM and no other features of HHT with a heterozygous missense (p.Gly291Ser), which is present in 20 hets in gnomAD v2.1. 1 family - PMID: 34611981 - a suspected HHT case and affected mother had heterozygous missense variant (p.Glu355Gln). Another suspected HHT case had another heterozygous missense variant (p.Val403Ile), but there are 23 hets in gnomAD v2.1. Also, 2 cases with multi-gene deletions including GDF2. 1 family - https://doi.org/10.1164/ajrccm-conference.2020.201.1_MeetingAbstracts.A6356 - A novel heterozygous GDF2 missense variant was identified in one HHT family from the 100,000 Genomes Project and segregated with disease. The proband was severely affected, having presented in childhood with multiple PAVMs, frequent epistaxis, and typical HHT telangiectasia. Plasma samples form the family showed significantly lower circulating BMP9 levels in affected cars compared to controls 3 homozygous cases with features of HHT, including PAVM: 2 probands - PMID: 33834622 - 2 unrelated paediatric cases with homozygous nonsense variants (p.Gln26Ter, p.Glu279Ter) with facial telangiectases and either pulmonary arterial hypertension or pulmonary arteriovenous malformations (PAVM). Plasma levels of both BMP9 and BMP10 were undetectable. Heterozygous parents did not have any symptoms or clinical signs of HHT. 1 proband - PMID: 32669404 - an 8 yo with epistaxis and diffuse PAVM homozygous for c.1060_1062delinsAG, p.Tyr354ArgfsTer15 (consanguineous family). 7 yo sister homozygous for the same variant had no symptoms, except some telangiectasia. Heterozygous parents had telangiectasia or epistaxis 2 supporting knockout animal models: PMID: 26056270 - knockout mouse model had imperfect closure of ductus arteriosus (an arterial connection in the foetus that directs blood flow away from the pulmonary circulation) PMID: 23972370 - BMP9 knockdown experiments in zebrafish exhibited small but significant decreases in both anterior-posterior and dorsal-ventral axes, as well as subtle defects in the maturation of the caudal vein.; Changed rating: GREEN; Changed publications: 23972370, 27081547, 32573726, 32992168, 34611981, 33834622, 32669404, 26056270, 23972370, https://doi.org/10.1164/ajrccm-conference.2020.201.1_MeetingAbstracts.A6356; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Hereditary Haemorrhagic Telangiectasia v0.12 | ENG | Zornitza Stark Marked gene: ENG as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Haemorrhagic Telangiectasia v0.12 | ENG | Zornitza Stark Gene: eng has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Haemorrhagic Telangiectasia v0.12 | ENG | Zornitza Stark reviewed gene: ENG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Telangiectasia, hereditary hemorrhagic, type 1, MIM# 187300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Haemorrhagic Telangiectasia v0.0 | ENG |
Bryony Thompson gene: ENG was added gene: ENG was added to Hereditary Haemorrhagic Telangiectasia_RMH. Sources: Expert Review Green,Royal Melbourne Hospital Mode of inheritance for gene: ENG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: ENG were set to Telangiectasia, hereditary hemorrhagic, type 1, 187300; Gastrointestinal telangiectasia (HP:0002604); Palate telangiectasia (HP:0002707); Lip telangiectasia (HP:0000214); Pulmonary arteriovenous malformation (HP:0006548); Nasal mucosa telangiectasia (HP:0000434); Tongue telangiectasia (HP:0000227); Epistaxis (HP:0000421); Cerebral arteriovenous malformation (HP:0002408); Hepatic arteriovenous malformation (HP:0006574; Spinal arteriovenous malformation (HP:0002390); ); Finger pad telangiectasia (pulp not nail side); Arteriovenous malformation (HP:0100026) |
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