BRIEF REPORT A Dystroglycan Mutation Associated with Limb-Girdle Muscular Dystrophy

被引：183

作者：

Hara, Yuji ^{[1
]}

Balci-Hayta, Burcu ^{[5
]}

Yoshida-Moriguchi, Takako ^{[1
]}

Kanagawa, Motoi ^{[1
]}

de Bernabe, Daniel Beltran-Valero ^{[1
]}

Gundesli, Hulya ^{[5
]}

Willer, Tobias ^{[1
]}

Satz, Jakob S. ^{[1
]}

Crawford, Robert W. ^{[1
]}

Burden, Steven J. ^{[8
]}

Kunz, Stefan ^{[9
,10
]}

Oldstone, Michael B. A. ^{[11
]}

Accardi, Alessio ^{[1
]}

Talim, Beril ^{[6
]}

Muntoni, Francesco ^{[12
]}

Topaloglu, Haluk ^{[7
]}

Dincer, Pervin ^{[5
]}

Campbell, Kevin P. ^{[1
,2
,3
,4
]}

机构：

[1] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Mol Physiol & Biophys, Iowa City, IA 52242 USA

[2] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Neurol, Iowa City, IA 52242 USA

[3] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Internal Med, Iowa City, IA 52242 USA

[4] Univ Iowa, Roy J & Lucille A Carver Coll Med, Howard Hughes Med Inst, Iowa City, IA 52242 USA

[5] Hacettepe Univ, Fac Med, Dept Med Biol, TR-06100 Ankara, Turkey

[6] Hacettepe Univ, Fac Med, Dept Pediat Pathol, TR-06100 Ankara, Turkey

[7] Hacettepe Univ, Fac Med, Dept Pediat Neurol, TR-06100 Ankara, Turkey

[8] NYU, Sch Med, Helen L & Martin S Kimmel Ctr Biol & Med, Skirball Inst Biomol Med,Mol Neurobiol Program, New York, NY USA

[9] Univ Lausanne, Lausanne, Switzerland

[10] Univ Hosp Ctr, Inst Microbiol, Lausanne, Switzerland

[11] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA USA

[12] UCL, Inst Child Hlth, Dubowitz Neuromuscular Ctr, London, England

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2011年 / 364卷 / 10期

基金：

美国国家卫生研究院;

关键词：

WALKER-WARBURG-SYNDROME; ALPHA-DYSTROGLYCAN; DEFECTIVE GLYCOSYLATION; ABNORMAL GLYCOSYLATION; MENTAL-RETARDATION; PROTEIN GENE; FORM; GLYCOSYLTRANSFERASE; EXPRESSION; DELETION;

D O I：

10.1056/NEJMoa1006939

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Dystroglycan, which serves as a major extracellular matrix receptor in muscle and the central nervous system, requires extensive O-glycosylation to function. We identified a dystroglycan missense mutation (Thr192. Met) in a woman with limb-girdle muscular dystrophy and cognitive impairment. A mouse model harboring this mutation recapitulates the immunohistochemical and neuromuscular abnormalities observed in the patient. In vitro and in vivo studies showed that the mutation impairs the receptor function of dystroglycan in skeletal muscle and brain by inhibiting the post-translational modification, mediated by the glycosyltransferase LARGE, of the phosphorylated O-mannosyl glycans on a-dystroglycan that is required for high-affinity binding to laminin.

引用

页码：939 / 946

页数：8

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