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


Hara Y., Balci-Hayta B., Yoshida-Moriguchi T., Kanagawa M., de Bernabe D. B. , Gundesli H., ...Daha Fazla

NEW ENGLAND JOURNAL OF MEDICINE, cilt.364, ss.939-946, 2011 (SCI İndekslerine Giren Dergi) identifier identifier

  • Cilt numarası: 364 Konu: 10
  • Basım Tarihi: 2011
  • Doi Numarası: 10.1056/nejmoa1006939
  • Dergi Adı: NEW ENGLAND JOURNAL OF MEDICINE
  • Sayfa Sayıları: ss.939-946

Özet

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.