Rinsho Shinkeigaku (Clinical Neurology)

The 43rd Annual Meeting of the Japanese Society of Neurology

Educational Lecture VIII:
Dystroglycan linkage and muscular dystrophy

Teruo Shimizu, M.D.

Department of Neurology, Teikyo University School of Medicine

Dystroglycan is a key complex between basal lamina laminin, extracellularly and membrano-cytoskeleton, intracellularly. The damage of this linkage is turned out to cause muscular dystrophies. Dystroglycan knockout is lethal. Dystroglycan-associated intracellular proteins such as dystrophin, dystrobrevin, sarcoglycans, plectin and caveolin-3 are responsible for causing severe (Duchenne type) and moderate forms (Becker, LGMDs). Laminin, dystroglycan-binding extracellular protein, is deficient in the most severe form of congenital muscular dystrophy with normal intelligence and eye. Recently, a remarkable progress is made in most severe forms of congenital muscular dystrophy with anomalies of brain and eye such as Fukuyama type (Japan) and muscle-eye-brain disease (Finland). The gene product for Fukuyama type, fukutin, belongs to a family of glycosylation enzymes in bacteria and yeast. Since α-dystroglycan contains 14∼15 o-glycans, ser/thr-mannose 2∼1 GlcNAc 4∼1 Gal 3∼2 Sial in the middle third mucin domain and the sial-o-glycan is essential for laminin-binding, and since α-dystroglycan is defective in Fukuyama type sarcolemma with anti both sugar moiety- and peptide-antidodies, defective fukutin causes incomplete o-glycosylation of α-dystroglycan. In '02, it is clarified that a glycosylation enzyme, POMGnT1 which modifies GlcNAc onto ser/thr-mannose, is defective in 6 MEB patients. The loss of the enzyme activity is turned out to lose α -dystroglycan from sarcolemma of MEB. These data strongly suggests that o-glycosylation defect of α-dystroglycan causes the most severe congenital muscular dystrophy such as Fukuyama type, MEB and Walker Warburg syndrome.

(CLINICA NEUROL, 42: 1091|1094, 2002)
key words: laminin-dystroglycan complex-dystrophin linkage, o-glycan of dystroglycan, severe muscular dystrophy, congenital muscular dystrophy

(Received: 31-May-02)