Cerebral vascular malformations
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.Created: 3 Dec 2019, 2:02 p.m. | Last Modified: 3 Dec 2019, 2:02 p.m.
Panel Version: 1.70
Comment on list classification: Mutations identified in nine families with intracerebral aneurysms. Good animal models support this resultCreated: 15 Dec 2016, 9:45 a.m.
Novel associated reported in PMID: 27895300 - segregation of the R450X variant was reported in all affected members of a large family with an logarithm of odds (LOD) score of 4.69 (disease frequency =0.032; penetrance=100%; R450X allele frequency=0.001). The variant was heterozygous in all affected people, obligate carriers, and 3 members with unknown clinical status. The mutation was absent in unaffected relatives, the control cohort (n=305), and 89040 chromosomes in the ExAC database. Variants found in 507 unrelated patients were enriched versus those in ExAC - In 8 unrelated probands, including those with sporadic disease, THSD1 missense mutations were identified that either exist in the signal peptide (L5F in 2 probands) or cluster in the intracellular region (R460W, E466G, G600E, P639L, T653I, and S775P). In a zebrafish model, loss of thsd1 caused intracranial hemorrhages by 48 hours. In a subset of mutant mice, brain magnetic resonance imagings revealed mild to severe dilatation of cerebral ventricles, consistent with hydrocephalus as young as 8 weeks.Created: 14 Dec 2016, 2:52 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
subarachnoid hemorrhage
Publications
Source Expert Review Amber was added to THSD1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Source Yorkshire and North East GLH was added to THSD1.
Source NHS GMS was added to THSD1.
Promoted to version 1 on the 19th December 2016
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
THSD1 was added to Cerebrovascular disorderspanel. Sources: Literature
THSD1 was created by ellenmcdonagh