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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Spectrum of HSPG2 (perlecan) mutations in patients with Schwartz-Jampel syndrome
Human Mutation, Volume 27, No. 11, Year 2006
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Description
Schwartz-Jampel syndrome (SJS) is a rare autosomal recessive condition denned by the association of myotonia with chondrodysplasia. SJS results from mutations in the HSPG2 gene, which encodes perlecan, a major component of basement membranes. Only eight HSPG2 mutations have been reported in six SJS families. Here, we describe the molecular findings in 23 families (35 patients) with SJS, being one-third of the SJS cases reported in the medical literature. We identified 22 new HSPG2 mutations and unreported polymorphisms. Mutations included nine deletion or insertion (41%), six splice site (27%), five missense (23%), and two nonsense mutations (9%). All but four mutations were private, and we found no evidence for a founder effect. Analyses of HSPG2 messenger RNA (mRNA) and perlecan immunostaining on patients' cells revealed a hypomorphic effect of the studied mutations. They also demonstrated distinct consequences of truncating and missense mutations on perlecan expression as truncating mutations resulted in instability of HSPG2 mRNA through nonsense mRNA-mediated decay, whereas missense mutations involving cysteine residues led to intracellular retention of perlecan, probably due to quality control pathways. Our analyses strengthen the idea that SJS results from hypomorphic mutations of the HSPG2 gene. They also propose tools for its molecular diagnosis and provide new clues for the understanding of its pathophysiology. © 2006 Wiley-Liss, Inc.
Authors & Co-Authors
Stum, Morgane
France, Paris
Inserm
France, Paris
Sorbonne Université
Davoine, Claire Sophie
France, Paris
Inserm
France, Paris
Sorbonne Université
Vicart, Savine
France, Paris
Inserm
France, Paris
Sorbonne Université
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Guillot-Noël, Léna
France, Paris
Inserm
France, Paris
Sorbonne Université
Topaloglu, Haluk A.
Turkey, Ankara
Hacettepe Üniversitesi
Carod-Artal, Francisco Javier
Brazil, Brasilia
Sarah Network of Rehabilitation Hospitals
Kayserili, Hülya U.
Turkey, Istanbul
İstanbul Tıp Fakültesi
Hentati, F. F.
Tunisia, Tunis
Institut National de Neurologie Mongi-ben Hamida
Merlini, Luciano
Italy, Ferrara
University of Ferrara
Urtizberea, Jean Andoni M.
France, Marin
Hôpital Marin
Hammouda, El Hadi
France, Evry
Généthon
Quan, Phuccanh
France, Paris
Inserm
France, Paris
Sorbonne Université
Fontaine, Bertrand
France, Paris
Inserm
France, Paris
Sorbonne Université
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Nicole, Sophie
France, Paris
Inserm
France, Paris
Sorbonne Université
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Statistics
Citations: 106
Authors: 14
Affiliations: 10
Identifiers
Doi:
10.1002/humu.20388
ISSN:
10597794
Research Areas
Genetics And Genomics