Congenital muscular dystrophy with glycosylation defects of alpha-dystroglycan in Japan

Hiroshi Matsumoto; Yukiko K Hayashi; Dae-Son Kim; Megumu Ogawa; Terumi Murakami; Satoru Noguchi; Ikuya Nonaka; Tomoyuki Nakazawa; Takiko Matsuo; Satoshi Futagami; Kevin P Campbell; Ichizo Nishino

doi:10.1016/j.nmd.2005.01.009

Congenital muscular dystrophy with glycosylation defects of alpha-dystroglycan in Japan

Neuromuscul Disord. 2005 May;15(5):342-8. doi: 10.1016/j.nmd.2005.01.009.

Authors

Hiroshi Matsumoto¹, Yukiko K Hayashi, Dae-Son Kim, Megumu Ogawa, Terumi Murakami, Satoru Noguchi, Ikuya Nonaka, Tomoyuki Nakazawa, Takiko Matsuo, Satoshi Futagami, Kevin P Campbell, Ichizo Nishino

Affiliation

¹ Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.

PMID: 15833426
DOI: 10.1016/j.nmd.2005.01.009

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Blotting, Western
Brain / pathology
Brain / physiopathology
Child, Preschool
DNA Mutational Analysis
Dystroglycans / deficiency*
Dystroglycans / genetics
Electroencephalography / methods
Female
Glycosylation
Guanine Nucleotide Exchange Factors / genetics
Guanine Nucleotide Exchange Factors / metabolism
Humans
Immunohistochemistry / methods
Infant
Japan / epidemiology
Magnetic Resonance Imaging / methods
Male
Mannosyltransferases / genetics
Mannosyltransferases / metabolism
Membrane Proteins
Muscle, Skeletal / metabolism
Muscle, Skeletal / pathology
Muscle, Skeletal / physiopathology
Muscular Dystrophies / genetics
Muscular Dystrophies / metabolism*
Muscular Dystrophies / physiopathology
Mutation
N-Acetylglucosaminyltransferases / genetics
N-Acetylglucosaminyltransferases / metabolism
Pentosyltransferases
Polymorphism, Single-Stranded Conformational
Proteins / genetics
Proteins / metabolism
Rho Guanine Nucleotide Exchange Factors
Staining and Labeling / methods

Substances

ARHGEF12 protein, human
FKTN protein, human
Guanine Nucleotide Exchange Factors
Membrane Proteins
Proteins
Rho Guanine Nucleotide Exchange Factors
Dystroglycans
Mannosyltransferases
N-Acetylglucosaminyltransferases
protein O-mannose beta-1,2-N-acetylglucosaminyltransferase
protein O-mannosyltransferase
FKRP protein, human
Pentosyltransferases