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| Cerebral vascular malformations v3.22 | ANO1 | Sarah Leigh edited their review of gene: ANO1: Added comment: Three ANO1 variant have been associated with Moyamoya disease 7 (OMIM:620687) in three unrelated cases (PMID: 37253099). Two of the variants were heterozygous in the patients, while the third was homozygous. For each of the variants, electrophysiologic studies in variant transfected HEK293 cells revealed that the variant channel had an increased Ca(2+) sensitivity resulting in increased membrane Cl- conductance at lower intracellular Ca(2+) levels in comparison to the controls, which is consistent with a gain-of-function effect.; Changed rating: GREEN; Changed publications to: 37253099; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v3.18 | ANO1 |
Alexandra Njegic gene: ANO1 was added gene: ANO1 was added to Cerebral vascular malformations. Sources: Literature Mode of inheritance for gene: ANO1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: ANO1 were set to 37253099; 37012328 Phenotypes for gene: ANO1 were set to Moyamoya disease 7, 620687 Penetrance for gene: ANO1 were set to Incomplete Mode of pathogenicity for gene: ANO1 was set to Other Review for gene: ANO1 was set to AMBER Added comment: 37253099: 6 families showed AD, 1 patient AR. GOF and LOF implied. 7 variants identified total from 84 unsolved families and additional 150 probands. In vitro modelling of different missense variants in HEK cells shows GOF and LOF mechanisms. GOF variants (p.Met658Val, p.Glu459Lys, p.Thr740Ile p.Glu170Lys) have increased membrane Cl− conductance at lower intracellular Ca2+ levels, determined through patch clamp. Predicted LOF p.Arg890Gln (in gnomAD) as no Ca2+ currents evoked. Some variants show no alteration to Ca2+ sensitivity (p.Arg77Gln [in gnomAD) and p.Ser196Thr) but near binding site for PIP2. Authors note that ANO1 may be paternally imprinted as affected individuals who inherited the variant from their mothers had an earlier age at onset, whereas those who inherited the variant from their father had later onset (families MM137/MM001). 37012328: 88 paediatric MMA patients, 3 patients with mixed clinical presentations had ANO1 variants through WES filtering, no evidence of pathogenicity provided. Sources: Literature |
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| Cerebral vascular malformations v1.70 | THSD1 | Louise Daugherty commented on gene: THSD1: Downgraded from Green to Amber. Combined reviews: Ian Berry (YNELGH) & GEL clinical team (Richard Scott & Helen Brittain) - Amber in view intracerebral aneurysms. Unclear on penetrance. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.67 | ACE | Louise Daugherty Source Yorkshire and North East GLH was added to ACE. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | ACE | Louise Daugherty Source NHS GMS was added to ACE. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations | ACE | Alice Gardham marked ACE as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations | ACE | Alice Gardham reviewed ACE | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||