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: 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
• Journal: Neuromuscular disorders : NMD (Neuromuscul Disord) Vol. 15 Issue 5 Pg. 342-8 (May 2005) ISSN: 0960-8966 [Print] England
• PMID: 15833426 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

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