A Dystroglycan Mutation Associated with Limb-Girdle Muscular Dystrophy

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 . . .