Publication
Title
COL5A1 Signal Peptide Mutations Interfere with Protein Secretion and Cause Classic Ehlers-Danlos Syndrome
Author
Abstract
Classic Ehlers-Danlos syndrome (EDS) is a heritable connective tissue disease characterized by skin hyperextensibility, atrophic scarring, joint hypermobility and generalized tissue fragility. Mutations in COL5A1 and COL5A2, encoding the type V collagen pro alpha 1- and pro alpha 2-chain, are found in similar to 50% of patients with classic EDS. The majority of mutations lead to a non-functional COL5A1 allele, as a result of the introduction of a premature stopcodon in one COL5A1 transcript. A minority of mutations affect the structure of the type V collagen central helical domain. We show that mutations in the signal peptide (SP) domain of the prepro alpha 1(V)-collagen chain cause classic EDS. The missense mutations (p.L25R and p.L25P) are located in the crucial hydrophobic SP core, which is indispensible for preprotein translocation into the endoplasmic reticulum. As a result, mutant type V procollagen is retained within the cell, leading to a decreased amount of type V collagen in the extracellular matrix and disturbed collagen fibrillogenesis. Our findings further support the observation that decreased availability of type V (pro) collagen is a key factor and a shared mechanism in the pathogenesis of classic EDS. (C) 2008 Wiley-Liss, Inc.
Language
English
Source (journal)
Human mutation. - New York, N.Y.
Publication
New York, N.Y. : 2009
ISSN
1059-7794
Volume/pages
30 :2 (2009) , p. E395-E403
ISI
000279979200008
Full text (Publisher's DOI)
UAntwerpen
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 05.11.2018
Last edited 07.10.2021