Aortopathy_Connective Tissue Disorders

Gene: COL5A1

Green List (high evidence)

Multifocal fibromuscular dysplasia (FMDMF) is characterized histologically by medial fibroplasia and angiographically by multiple arterial stenoses with intervening mural dilations. Arterial tortuosity, macroaneurysms, dissections, and rupture may occur.

4 unrelated individuals reported, but all had the same variant, p.Gly514Ser, and haplotype analysis was consistent with founder effect. Further rare missense variants were identified in a cohort, although limited information available.

Created: 19 May 2021, 11:40 p.m. | Last Modified: 19 May 2021, 11:40 p.m.

Panel Version: 1.30

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Fibromuscular dysplasia, multifocal, MIM# 619329

Publications

• 32938213

Green List (high evidence)

PMID: 30071989; Classified as 'No Evidence' by Clingen for heritable thoracic aortic aneurysm and dissection


GeneReviews: 75-78% of classical EDS is caused by pathogenic variants in COL5A1. Haploinsufficiency is the more common disease mechanism whoeever, missense variants in the triple helical domain of the α1(V) or α2(V) chains are likely to have dominant-negative activity.
(https://www.ncbi.nlm.nih.gov/books/NBK1244/)

Created: 25 Jun 2020, 3:16 a.m. | Last Modified: 25 Jun 2020, 3:16 a.m.

Panel Version: 0.26

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Heritable Thoracic Aortic Aneurysm and Dissection; Classic Ehlers-Danlos Syndrome (MIM# 130000)

Publications

• PMID: 30071989