Extracellular matrix and platelet function in patients with musculocontractural Ehlers-Danlos syndrome caused by mutations in the CHST14 gene.

Details

Serval ID
serval:BIB_24D53E9B6808
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Extracellular matrix and platelet function in patients with musculocontractural Ehlers-Danlos syndrome caused by mutations in the CHST14 gene.
Journal
American Journal of Medical Genetics. Part A
Author(s)
Mendoza-Londono R., Chitayat D., Kahr W.H., Hinek A., Blaser S., Dupuis L., Goh E., Badilla-Porras R., Howard A., Mittaz L., Superti-Furga A., Unger S., Nishimura G., Bonafe L.
ISSN
1552-4833 (Electronic)
ISSN-L
1552-4825
Publication state
Published
Issued date
2012
Volume
158A
Number
6
Pages
1344-1354
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
We report on a consanguineous, Afghani family with two sisters affected with characteristic facial features, multiple contractures, progressive joint and skin laxity, hemorrhagic diathesis following minor trauma and multisystem fragility-related manifestations suggestive of a diagnosis of musculocontractural Ehlers-Danlos syndrome (EDS). This novel form of connective tissue disorder was recently reported in patients of Japanese, Turkish, and Indian descent who were formerly classified as having EDS type VIB and has now been recognized to be a part of spectrum including patients previously classified as having adducted thumb-clubfoot syndrome. We identified a previously unreported mutation in the CHST14 gene, which codes for the enzyme dermatan 4-O-sulfotransferase. We discuss the prenatal presentation, detailed clinical manifestations, and neurological findings in two sisters with this newly described musculocontractural EDS-CHST14 type. We demonstrate that fibroblasts from one of our patients produce more chondroitin sulfate than normal and show lower than normal deposition of collagens I and II and fibrillin 1-containing microfibrills. These findings suggest that the imbalance in the glycosaminoglycan content in developing tissues might interfere with normal deposition of other extracellular matrix components and ultimately contribute to the development of the phenotype observed in these patients. Furthermore, we ruled out the contribution of intrinsic platelet factors to the bleeding diathesis observed in some affected individuals. © 2012 Wiley Periodicals, Inc.
Pubmed
Web of science
Create date
14/06/2012 17:20
Last modification date
20/08/2019 13:03
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