Skeletal dysplasia

Gene: COL5A1

Green List (high evidence)

The association with classic EDS is well established. 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.

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. Association with this disease entity has moderate-limited evidence.

Created: 19 May 2021, 11:42 p.m. | Last Modified: 19 May 2021, 11:42 p.m.

Panel Version: 0.7648

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Ehlers-Danlos syndrome, classic type, 1, MIM# 130000; Fibromuscular dysplasia, multifocal, MIM# 619329

Publications

• 30071989
• 32938213