title: Dysferlin aggregation in limb-girdle muscular dystrophy type 2B/Miyoshi Myopathy necessitates mutational screen for diagnosis [corrected].
abstract: BACKGROUND
  Diagnosis of the limb-girdle muscular dystrophies (LGMDs) has been facilitated by the use of immunofluorescence microscopy, Western blot analysis, and rapid genetic testing.
  
  
  METHODS
  We identified 7 patients with LGMD2B or Miyoshi myopathy (MM) phenotypes and performed detailed history, physical examination, and mutation analyses of genomic DNA.
  
  
  RESULTS
  Ten disease-causing variants of the dysferlin gene (DYSF) were detected, 4 of which were novel and predicted to be pathogenic (IVS33+9G>T, c.1343T>C, c.4747T>G, and c.5066dupC). Two of these mutations (c.1343T>C and IVS33+9G>T) were associated with a reduction in sarcolemmal dysferlin expression, despite increased total mRNA and protein in mixed muscle homogenates, due to a pathological retention of the mutated polypeptide in the cytoplasm.
  
  
  CONCLUSIONS
  Considering that protein-based assays may yield false negative test results and that dysferlin aggregation may be present in other LGMDs, mutational screening is necessary for specific diagnosis in primary dysferlinopathy patients exhibiting this phenotype.
authors.affiliation: Department of Pediatrics and Medicine, Neuromuscular Clinic, McMaster University Hospital, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Mats I
authors.initials: MI
authors.lastname: Nilsson
authors.forename: Marissa L
authors.initials: ML
authors.lastname: Laureano
authors.forename: Munim
authors.initials: M
authors.lastname: Saeed
authors.forename: Mark A
authors.initials: MA
authors.lastname: Tarnopolsky
mesh_terms: D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis; D000073939:Dysferlin; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D049288:Muscular Dystrophies, Limb-Girdle / Q000175:diagnosis* / Q000235:genetics; D009154:Mutation; D010641:Phenotype
chemical_list: C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins