A Dystroglycan Mutation Associated with Limb-Girdle Muscular Dystrophy

• Published in: The New England journal of medicine Vol. 364; no. 10; pp. 939 - 946
• Main Authors: Hara, Yuji, Balci-Hayta, Burcu, Yoshida-Moriguchi, Takako, Kanagawa, Motoi, Beltrán-Valero de Bernabé, Daniel, Gündeşli, Hülya, Willer, Tobias, Satz, Jakob S, Crawford, Robert W, Burden, Steven J, Kunz, Stefan, Oldstone, Michael B.A, Accardi, Alessio, Talim, Beril, Muntoni, Francesco, Topaloğlu, Haluk, Dinçer, Pervin, Campbell, Kevin P
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 10.03.2011
• Subjects: Animals; Biological and medical sciences; Disease Models, Animal; Dystroglycans - genetics; Female; General aspects; Humans; Medical sciences; Mice; Muscular Dystrophies, Limb-Girdle - genetics; Mutation, Missense; Pedigree; Phenotype; Sequence Analysis, DNA; Medicine; Dystroglycan; Association; Limb girdle muscular dystrophy; Genetics; Mutation; Biological receptor
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1006939

A dystroglycan mutation was identified in a patient with limb-girdle muscular dystrophy and cognitive dysfunction. A mouse model with this mutation reproduced features of the disease phenotype. This work extends our knowledge of the causes of limb-girdle muscular dystrophy. Muscular dystrophies are genetic diseases characterized by weakness and progressive degeneration of skeletal muscle. The transmembrane protein dystroglycan, which is ultimately cleaved into an α and a β component, is a key link between the cytoskeleton and extracellular-matrix proteins that bear laminin globular domains (e.g., laminin, agrin, and neurexin). 1 , 2 The mucin domain of α-dystroglycan is modified with numerous O-linked oligosaccharides that are essential for its normal function as an extracellular-matrix receptor in various tissues, including skeletal muscle and brain. 2 , 3 Hypoglycosylation of α-dystroglycan and a consequent reduction of α-dystroglycan binding to extracellular-matrix proteins are observed in patients with the . . .