title: [Gene analysis in patients with muscular dystrophy: alpha-sarcoglycan (adhalin) gene mutations in patients with malignant limb-girdle muscular dystrophy].
abstract: Malignant limb-girdle muscular dystrophy (MLGMD) was proposed by Miyoshi et al. in 1966 as a clinical and genetic entity of muscular dystrophy, with clinical features similar to Duchenne muscular dystrophy but showing autosomal recessive inheritance. Recently, deficiency of alpha-sarcoglycan (adhalin), which is one of the components of dystrophin-glycoprotein complex, in the skeletal muscle has been found in several patients with MLGMD or severe childhood autosomal recessive muscular dystrophy. To investigate alpha-sarcoglycan gene mutations in patients with MLGMD, we analyzed cDNA prepared from skeletal muscle by reverse transcription polymerase chain reaction (RT-PCR), or genomic DNA prepared from peripheral blood leukocytes by PCR, using single-strand conformation polymorphism (SSCP). When products amplified by RT-PCR or PCR showed aberrant conformers on SSCP analysis, these products were sequenced by the fluorescence-based dideoxy termination method. We found missense mutations, insertions or deletions in the alpha-sarcoglycan gene in 6 families with MLGMD. In the literature, alpha-sarcoglycan gene mutations have been identified in 21 families with MLGMD/SCARMD including our 6 families. Half of the families have the cytosine to thymidine substitution at nt.229, resulting in the replacement of Arg by Cys at codon 77, and most of the mutations have been found in the region coding extracellular domain of alpha-sarcoglycan. Analysis of the alpha-sarcoglycan gene is indispensable for diagnosis, assessment of prognosis, genetic counseling, and future gene therapy in patients with autosomal recessive childhood-onset muscular dystrophy.
authors.affiliation: First Department of Internal Medicine, School of Medicine, University of Tokushima.
authors.forename: M
authors.initials: M
authors.lastname: Akaike
authors.forename: H
authors.initials: H
authors.lastname: Kawai
mesh_terms: D003598:Cytoskeletal Proteins / Q000235:genetics*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D009136:Muscular Dystrophies / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D049031:Sarcoglycans
chemical_list: D003598:Cytoskeletal Proteins; D008562:Membrane Glycoproteins; D049031:Sarcoglycans