Journal article
A Dystroglycan Mutation Associated with Limb-Girdle Muscular Dystrophy
The New England journal of medicine, Vol.364(10), pp.939-946
2011
DOI: 10.1056/NEJMoa1006939
PMCID: PMC3071687
PMID: 21388311
Abstract
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 α-dystroglycan that is required for high-affinity binding to laminin.
Details
- Title: Subtitle
- A Dystroglycan Mutation Associated with Limb-Girdle Muscular Dystrophy
- Creators
- Yuji HARA - Department of Molecular Physiology and Biophysics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, United StatesBurcu BALCI-HAYTA - Department of Medical Biology, Faculty of Medicine, Hacettepe University, Sihhiye, Ankara, TurkeyStefan KUNZ - Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, SwitzerlandMichael B. A OLDSTONE - Department of Immunology and Microbial Science, Scripps Research Institute, La Jolla, CA, United StatesAlessio ACCARDI - Department of Molecular Physiology and Biophysics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, United StatesBeril TALIM - Department of Pediatric Pathology, Faculty of Medicine, Hacettepe University, Sihhiye, Ankara, TurkeyFrancesco MUNTONI - Dubowitz Neuromuscular Centre, University College London Institute of Child Health, London, United KingdomHaluk TOPALOGLU - Department of Pediatric Neurology, Faculty of Medicine, Hacettepe University, Sihhiye, Ankara, TurkeyPervin DINCER - Department of Medical Biology, Faculty of Medicine, Hacettepe University, Sihhiye, Ankara, TurkeyKevin P CAMPBELL - Department of Molecular Physiology and Biophysics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, United StatesTakako YOSHIDA-MORIGUCHI - Department of Molecular Physiology and Biophysics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, United StatesMotoi KANAGAWA - Department of Molecular Physiology and Biophysics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, United StatesDaniel Beltrán-Valero DE BERNABE - Department of Molecular Physiology and Biophysics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, United StatesHülya GÜNDESLI - Department of Medical Biology, Faculty of Medicine, Hacettepe University, Sihhiye, Ankara, TurkeyTobias WILLER - Department of Molecular Physiology and Biophysics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, United StatesJakob S SATZ - Department of Molecular Physiology and Biophysics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, United StatesRobert W CRAWFORD - Department of Molecular Physiology and Biophysics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, United StatesSteven J BURDEN - Molecular Neurobiology Program, Helen L. and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University Medical School, New York, United States
- Resource Type
- Journal article
- Publication Details
- The New England journal of medicine, Vol.364(10), pp.939-946
- Publisher
- Massachusetts Medical Society; Waltham, MA
- DOI
- 10.1056/NEJMoa1006939
- PMID
- 21388311
- PMCID
- PMC3071687
- ISSN
- 0028-4793
- eISSN
- 1533-4406
- Language
- English
- Date published
- 2011
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020897802771
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