A dystroglycan mutation associated with limb-girdle muscular dystrophy Academic Article uri icon

Overview

MeSH Major

  • Dystroglycans
  • Muscular Dystrophies, Limb-Girdle
  • Mutation, Missense

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.

publication date

  • March 10, 2011

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3071687

Digital Object Identifier (DOI)

  • 10.1056/NEJMoa1006939

PubMed ID

  • 21388311

Additional Document Info

start page

  • 939

end page

  • 46

volume

  • 364

number

  • 10