Thoracic aortic aneurysm or dissection (GMS)

Gene: SECISBP2

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 4 Dec 2024, 9:45 p.m. | Last Modified: 4 Dec 2024, 9:45 p.m.

Panel Version: 3.19

Comment on list classification: There is sufficient evidence available (four unrelated cases and animal models) for the promotion of this gene to green rating in the next GMS review.

Created: 10 Apr 2024, 5:56 p.m. | Last Modified: 10 Apr 2024, 5:56 p.m.

Panel Version: 3.11

PMID:38042913 reported the identification of four unrelated individuals with biallelic SECISBP2 variants and showed early-onset, progressive, aneurysmal dilatation of the ascending aorta due to cystic medial necrosis. In addition, zebrafish and mice with global or vascular smooth muscle cell (VSMC)-targeted disruption of Secisbp2 respectively showed similar aortopathy.

Created: 10 Apr 2024, 5:51 p.m. | Last Modified: 10 Apr 2024, 5:51 p.m.

Panel Version: 3.8

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Thyroid hormone metabolism, abnormal, 1, OMIM:609698

Publications

• 38042913

Green List (high evidence)

Biallelic defects in this gene cause a multi system disorder with deficiency of most human selenoproteins. Phenotypes listed here are associated with a biochemical signature of elevated circulating T4 (thyroxine) and low plasma selenium.

Since some pathogenic variants can be in non-coding regions and cryptic, we suggest a high index of suspicion even in cases of aortic aneurysm with an apparently monoallelic SECISBP2 defect. In such cases, we advocate measuring circulating T4 and selenium; if these biomarker levels are abnormal a cryptic mutation on the other allele should be sought.
Sources: Literature

Created: 28 Mar 2024, 6:06 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Growth retardation; sensorineural hearing loss; muscular dystrophy; thoracic aortic aneurysm; raised circulating thyroxine and low plasma selenium

Publications

• PMID 38042913
• PMID 21084748