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Thoracic aortic aneurysm or dissection (GMS) v3.17 THBS2 Arina Puzriakova Phenotypes for gene: THBS2 were changed from aortic dilatation and rupture; prolonged bleeding time; atrophic scarring, joint hypermobility and frequent joint dislocations to ?Ehlers-Danlos syndrome, classic-like, 3, OMIM:620865
Thoracic aortic aneurysm or dissection (GMS) v3.16 THBS2 Arina Puzriakova Publications for gene: THBS2 were set to https://doi.org/10.1038/s41431-024-01559-1
Thoracic aortic aneurysm or dissection (GMS) v3.15 THBS2 Arina Puzriakova Classified gene: THBS2 as Red List (low evidence)
Thoracic aortic aneurysm or dissection (GMS) v3.15 THBS2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Neeti Ghali (NWTRGS). Rating Red as only a single family has been reported to date (see below) but this is a good candidate for future promotion if additional cases are identified.

- PMID: 38433265 (2024) reports on a three-generation family of Ashkenazi Jewish ancestry with a previously uncharacterised connective tissue disorder with features of EDS with prominent vascular involvement, caused by a heterozygous pathogenic variant (c.2686T>C, p.Cys896Arg) in THBS2.
Thoracic aortic aneurysm or dissection (GMS) v3.15 THBS2 Arina Puzriakova Gene: thbs2 has been classified as Red List (Low Evidence).
Thoracic aortic aneurysm or dissection (GMS) v3.11 THBS2 Neeti Ghali gene: THBS2 was added
gene: THBS2 was added to Thoracic aortic aneurysm or dissection (GMS). Sources: Literature
Mode of inheritance for gene: THBS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: THBS2 were set to https://doi.org/10.1038/s41431-024-01559-1
Phenotypes for gene: THBS2 were set to aortic dilatation and rupture; prolonged bleeding time; atrophic scarring, joint hypermobility and frequent joint dislocations
Penetrance for gene: THBS2 were set to unknown
Mode of pathogenicity for gene: THBS2 was set to Other
Review for gene: THBS2 was set to RED
Added comment: For R125, I would consider this to be 'red' (ie low evidence at present) but with a view to observing for other publications. There is only one recently (March 2024) published family but mouse work was also described in this publication. The phenotype is described as a novel form of EDS with vascular features as well as musculoskeletal (joint hypermobility, tendon rupture and joint dislocations), haematological (prolonged bleeding) and dermatological features (atrophic scarring). One patient had cerebral aneurysms and died from an abdominal aorta dissection at the age of 70 (but therefore was not genetically confirmed) and one displayed an enlarged ascending aortic arch at 50 (4.2cm). Lifestyle factors were not discussed and the two younger relatives (30s) did not have aortopathy. Electron microscopy revealed abnormally disorganised collagen fibres. The variant described is a missense (Cys to Arg in highly conserved region) and a CRISPR/Cas9 knock-in mouse demonstrated phenotypic traits correlating with those observed in human subjects (but not aortopathy). Protein has been found to be mainly expressed in large blood vessels such as aorta.
Sources: Literature