title: [Diagnostic procedure of limb girdle muscular dystrophies 2A or calpainopathies: French cohort from a neuromuscular center (Bordeaux)].
abstract: BACKGROUND
  Limb girdle muscular dystrophies are rare genetic diseases. Despite constant progress in genetics and biochemistry, the pathogenic mechanisms are not completely understood. Calpainopathy (LGMD2A) has been reported to be the most frequent autosomal recessive form of muscular dystrophy in several populations. Point mutations in CAPN3 are difficult to identify and the analysis is long and costly. The use of western blot does not seem to provide the expected sensitivity and specificity.
  
  
  METHODS
  We studied all the patients diagnosed in the neuromuscular center of Bordeaux (France) with confirmed calpainopathy in order to establish the appropriate diagnostic approach (inclusion criteria: muscular biopsy with calpain 3 western blot study, two mutations in CAPN3). Patients with highly suspected calpainopathy (same criteria with only one mutation) were also analyzed.
  
  
  RESULTS
  Our 13 patients belonged to 10 different families. Four patients had a normal western blot for calpain (WBn). We found high phenotypic variability with frequent atypical signs. The WBn group had less severe disease (a statistically significant later age of onset, a tendency toward lower CK levels and a slower disease course). We extended this comparison to the single mutation patients and we found the same results.
  
  
  CONCLUSIONS
  Considering the lack of sensitivity of western blot protein analysis in LGMD2A, a normal western blot for calpain should not halt the genetic analysis. The western blot result seems to have prognostic value. A normal western blot may help genetic testing by highlighting some mutational hot spots in the CAPN3 gene.
authors.affiliation: Département de neurologie, centre de référence des maladies neuromusculaires, groupe hospitalier Sud, CHU de Bordeaux, 33600 Pessac, France. perezflorian@hotmail.com
authors.forename: F
authors.initials: F
authors.lastname: Perez
authors.forename: A
authors.initials: A
authors.lastname: Vital
authors.forename: M-L
authors.initials: ML
authors.lastname: Martin-Negrier
authors.forename: X
authors.initials: X
authors.lastname: Ferrer
authors.forename: G
authors.initials: G
authors.lastname: Sole
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015153:Blotting, Western; D002154:Calpain / Q000235:genetics / Q000502:physiology*; D002648:Child; D015331:Cohort Studies; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics; D049288:Muscular Dystrophies, Limb-Girdle / Q000175:diagnosis*; D009468:Neuromuscular Diseases / Q000175:diagnosis; D010641:Phenotype; D017354:Point Mutation; D011379:Prognosis; D055815:Young Adult
chemical_list: D009124:Muscle Proteins; C105884:CAPN3 protein, human; D002154:Calpain