title: Congenital muscular dystrophy with glycosylation defects of alpha-dystroglycan in Japan.
abstract: Glycosylation defects of alpha-dystroglycan (alpha-DG) cause various muscular dystrophies. We performed clinical, pathological and genetic analyses of 62 Japanese patients with congenital muscular dystrophy, whose skeletal muscle showed deficiency of glycosylated form of alpha-DG. We found, the first Japanese patient with congenital muscular dystrophy 1C with a novel compound heterozygous mutation in the fukutin-related protein gene. Fukuyama-type congenital muscular dystrophy was genetically confirmed in 54 of 62 patients. Two patients with muscle-eye-brain disease and one Walker-Warburg syndrome were also genetically confirmed. Four patients had no mutation in any known genes associated with glycosylation of alpha-DG. Interestingly, the molecular mass of alpha-DG in the skeletal muscle was similar and was reduced to approximately 90 kDa among these patients, even though the causative gene and the clinico-pathological severity were different. This result suggests that other factors can modify clinical features of the patients with glycosylation defects of alpha-DG.
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Yukiko K
authors.initials: YK
authors.lastname: Hayashi
authors.forename: Dae-Son
authors.initials: DS
authors.lastname: Kim
authors.forename: Megumu
authors.initials: M
authors.lastname: Ogawa
authors.forename: Terumi
authors.initials: T
authors.lastname: Murakami
authors.forename: Satoru
authors.initials: S
authors.lastname: Noguchi
authors.forename: Ikuya
authors.initials: I
authors.lastname: Nonaka
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Takiko
authors.initials: T
authors.lastname: Matsuo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Futagami
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Campbell
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
mesh_terms: D015153:Blotting, Western; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D049030:Dystroglycans / Q000172:deficiency* / Q000235:genetics; D004569:Electroencephalography / Q000379:methods; D005260:Female; D006031:Glycosylation; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007223:Infant; D007564:Japan / Q000453:epidemiology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008364:Mannosyltransferases / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009136:Muscular Dystrophies / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009154:Mutation; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D010430:Pentosyltransferases; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D064067:Rho Guanine Nucleotide Exchange Factors; D013194:Staining and Labeling / Q000379:methods
chemical_list: C577222:ARHGEF12 protein, human; C113587:FKTN protein, human; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; D011506:Proteins; D064067:Rho Guanine Nucleotide Exchange Factors; D049030:Dystroglycans; D008364:Mannosyltransferases; D017351:N-Acetylglucosaminyltransferases; C443106:protein O-mannose beta-1,2-N-acetylglucosaminyltransferase; C082696:protein O-mannosyltransferase; C443107:FKRP protein, human; D010430:Pentosyltransferases