Clinical and genetic features of 20 Japanese patients with vascular-type Ehlers-Danlos syndrome

Abstract

The analysis in the present series revealed a low frequency of patients presenting with serious clinical findings such as arterial rupture/arterial dissection/aneurysm and perforation or rupture of the gastrointestinal tract, and revealed a higher prevalence of splice-site mutations at the junction of the triple-helical exons than of glycine substitution mutations in COL3A1.

The extracellular matrix of the dermis: flexible structures with dynamic functions

“…Here, again some mutations (mostly splice site mutations) are likely to cause mRNA instability and nonsense‐mediated decay, while others (glycine substitutions) presumably hinder the folding of three collagen α1(III) chains into a triple helix (42,43). Interestingly, a recent study showed that both splice site and glycine substitution mutations resulted in a drastic reduction in the amount of collagen III at the protein level (44), supporting the notion that misfolded collagen trimers fail to pass the quality control in the endoplasmic reticulum and consequently are targeted for degradation (8,15). The outcome of both scenarios is that reduced amounts of an otherwise structurally normal collagen III are insufficient to form functionally correct collagen fibrils (Fig.…”

Diagnosis of vascular Ehlers-Danlos syndrome in Italy: Clinical findings and novel COL3A1 mutations

“…Three identical pro-a1(III) chains, consisting of a central collagenous domain with repeated [Gly-X-Y] 343 triplets and two flanking amino-and carboxy-terminal noncollagenous domains, are assembled into type III pro-collagen homotrimers. Approximately 200 mutations in the COL3A1 gene have been reported; the majority of these are missense mutations that substitute a glycine (68%), while 22% affect splice sites [3,4,7,8]. Approximately 200 mutations in the COL3A1 gene have been reported; the majority of these are missense mutations that substitute a glycine (68%), while 22% affect splice sites [3,4,7,8].…”

Treatment of Vascular Ehlers-Danlos Syndrome

“…92 Furthermore, there are spontaneous de novo mutations without a family history making a correct diagnosis even more difficult. There may also be racial differences.…”