[Recent advances in congenital muscular dystrophy research].
Congenital muscular dystrophy (CMD) is a group of heterogeneous disorders characterized clinically by delayed milestones due to generalized muscle weakness and dystrophic muscle pathology. The discovery of fukutin, responsible gene for Fukuyama CMD (FCMD) and defective glycosylation in its muscle biopsy has lead significant advances in CMD researches, especially disorders with glycosylation defects to a dystroglycan (alphaDG). The highly glycosylated a DG is one of the major dystrophin-associated proteins anchored a basement membrane protein, laminin 2 to the dystrophin molecule. The disorders with the defective glycosylation are now categorized as a dystroglycanopathies which include FCMD, muscle-eye-brain (MEB) disease, Walker-Warburg syndrome (WWS) and diseases with mutations in fukutin-related protein (FKRP) and LARGE genes. Among them, MEB and WWS were proven to have mutations in the glycosyltransferase genes, POMGnT1 (protein O-mannose beta 1,2-N-acetylglucosaminyl/transferase 1) and POMT1 (protein O-mannosyltransferase 1), respectively, though others are still unknown how the glycosylation defect is induced. Although the disease with FKRP mutation has variable phenotypes from CMD to limb-girdle muscular dystrophy, others with defective to decreased a DG show CMD, central nervous system involvement with migration disorder (polymicrogyria) and ocular abnormalities.
Nonaka
Ikuya
I
National Center Hospital for Mental, Mervous and Muscular Disorders, National Center of Neurology and Psychiatry, Kodaira, Tokyo. nonaka@ncnp.go.jp
D006801:Humans; D009136:Muscular Dystrophies / Q000145:classification* / Q000235:genetics