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Extracellular matrix and platelet function in patients with musculocontractural Ehlers–Danlos syndrome caused by mutations in the CHST14 gene
Author(s) -
MendozaLondono Roberto,
Chitayat David,
Kahr Walter H.A.,
Hinek Aleksander,
Blaser Susan,
Dupuis Lucie,
Goh Elaine,
BadillaPorras Ramses,
Howard Andrew,
Mittaz Laureane,
SupertiFurga Andrea,
Unger Sheila,
Nishimura Gen,
Bonafe Luisa
Publication year - 2012
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.35339
Subject(s) - ehlers–danlos syndrome , ectopia lentis , extracellular matrix , joint hypermobility , medicine , bleeding diathesis , genetics , pathology , biology , marfan syndrome , immunology , platelet , anatomy
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.