title: Mutations in the sarcoglycan genes in patients with myopathy.
abstract: BACKGROUND
  Some patients with autosomal recessive limb-girdle muscular dystrophy have mutations in the genes coding for the sarcoglycan proteins (alpha-, beta-, gamma-, and delta-sarcoglycan). To determine the frequency of sarcoglycan-gene mutations and the relation between the clinical features and genotype, we studied several hundred patients with myopathy.
  
  
  METHODS
  Antibody against alpha-sarcoglycan was used to stain muscle-biopsy specimens from 556 patients with myopathy and normal dystrophin genes (the gene frequently deleted in X-linked muscular dystrophy). Patients whose biopsy specimens showed a deficiency of alpha-sarcoglycan on immunostaining were studied for mutations of the alpha-, beta-, and gamma-sarcoglycan genes with reverse transcription of muscle RNA, analysis involving single-strand conformation polymorphisms, and sequencing.
  
  
  RESULTS
  Levels of alpha-sarcoglycan were found to be decreased on immunostaining of muscle-biopsy specimens from 54 of the 556 patients (10 percent); in 25 of these patients no alpha-sarcoglycan was detected. Screening for sarcoglycan-gene mutations in 50 of the 54 patients revealed mutations in 29 patients (58 percent): 17 (34 percent) had mutations in the alpha-sarcoglycan gene, 8 (16 percent) in the beta-sarcoglycan gene, and 4 (8 percent) in the gamma-sarcoglycan gene. No mutations were found in 21 patients (42 percent). The prevalence of sarcoglycan-gene mutations was highest among patients with severe (Duchenne-like) muscular dystrophy that began in childhood (18 of 83 patients, or 22 percent); the prevalence among patients with proximal (limb-girdle) muscular dystrophy with a later onset was 6 percent (11 of 180 patients).
  
  
  CONCLUSIONS
  Defects in the genes coding for the sarcoglycan proteins are limited to patients with Duchenne-like and limb-girdle muscular dystrophy with normal dystrophin and occur in 11 percent of such patients.
authors.affiliation: Department of Human Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Duggan
authors.forename: J R
authors.initials: JR
authors.lastname: Gorospe
authors.forename: M
authors.initials: M
authors.lastname: Fanin
authors.forename: E P
authors.initials: EP
authors.lastname: Hoffman
authors.forename: C
authors.initials: C
authors.lastname: Angelini
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002648:Child; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics*; D004252:DNA Mutational Analysis; D049030:Dystroglycans; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics*; D018482:Muscle, Skeletal; D009136:Muscular Dystrophies / Q000145:classification / Q000235:genetics*; D009154:Mutation; D009210:Myofibrils / Q000648:ultrastructure; D009468:Neuromuscular Diseases / Q000235:genetics*; D049031:Sarcoglycans
chemical_list: D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D008562:Membrane Glycoproteins; D049031:Sarcoglycans; D049030:Dystroglycans