2008 Volume 48 Issue 8 Pages 543-549
Congenital muscular dystrophy (CMD) refers to a heterogeneous group of muscular dystrophies with onset during the neonatal period. Among them, some types of CMD are characterized by the association of brain malformations and ocular abnormalities. Biochemical analyses revealed altered glycosylation and decreased laminin-binding activity of α-dystroglycan in these disorders, therefore they are correctively called α-dystroglycanopathy. Recently, mutations in the genes encoding demonstrated or putative glycosyltransferases have been identified in α-dystroglycanopathy. Fukuyama-type CMD and MDC1C are caused by mutations in the fukutin and fukutin-related protein (FKRP) genes, respectively. Mutations in the protein O-mannose β-1, 2-N-acetylglucosaminyltransferase (POMGnT-1) and protein O-mannosyltransferase 1 and 2 (POMT1 and POMT2) genes cause muscle-eye-brain disease and Walker-Warburg syndrome, respectively. In addition, mutations in Large gene results in MDC1D. Furthermore, recent genotype-phenotype correlation analyses have revealed that the spectrum of phenotypes caused by mutations in these genes is much wider than originally assumed. In this review, we focus on the molecular pathomechanism and diverging clinical phenotypes of α-dystroglycanopathy.
