title: Limb girdle muscular dystrophy type 2A in India: a study based on semi-quantitative protein analysis, with clinical and histopathological correlation.
abstract: BACKGROUND
  Limb girdle muscular dystrophy (LGMD) type 2A is caused by mutation in the gene encoding for calpain-3 resulting in total or partial loss of protein. Diagnosis of LGMD2A, the most prevalent form of LGMD, is established by analyzing calpain-3 protein deficiency or CAPN3 gene mutation. Since there is no data from India regarding the incidence of LGMD2A, this study was undertaken.
  
  
  OBJECTIVE
  To study the frequency of LGMD2A in Indian population on the basis of protein analysis by immunoblotting and to correlate pathological and clinical features with protein analysis.
  
  
  METHODS
  One hundred and seventy-one muscle biopsies of clinically suspected LGMD, unclassified muscular dystrophy or myopathy were analyzed in a tertiary national referral centre for neurosciences. Materials and Methods : Histopathological, immunohistochemical and enzyme histochemical analysis of muscle biopsies was performed followed by protein analysis for calpain-3 and dysferlin by immunoblotting.
  
  
  RESULTS
  Immunoblot identified 75 patients (43.8%) with calpain-3 deficiency, of which 36 (45%) had complete loss and 39 (55%) had partial loss of calpain-3 protein. In patients with LGMD phenotype alone, the incidence of LGMD2A was 47%. The biopsies of these patients displayed variety of morphological changes ranging from dystrophic pattern with presence of active fibre necrosis, regeneration and lobulated fibres to end stage muscle disease. The mean age of presentation and disease onset was 24 and 18 years respectively.
  
  
  CONCLUSIONS
  This series of 75 patients is probably the first confirmed cases of LGMD2A (calpainopathy) from India. Our study suggests that LGMD2A is the most frequent form of LGMD in India, similar to the Western data, thus, highlighting the importance of immunoblotting for an accurate diagnosis.
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Pathak
authors.forename: Mehar C
authors.initials: MC
authors.lastname: Sharma
authors.forename: Chitra
authors.initials: C
authors.lastname: Sarkar
authors.forename: Prerana
authors.initials: P
authors.lastname: Jha
authors.forename: Vaishali
authors.initials: V
authors.lastname: Suri
authors.forename: Husain
authors.initials: H
authors.lastname: Mohd
authors.forename: Sumit
authors.initials: S
authors.lastname: Singh
authors.forename: Rohit
authors.initials: R
authors.lastname: Bhatia
authors.forename: Sheffali
authors.initials: S
authors.lastname: Gulati
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002154:Calpain / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003402:Creatine Kinase / Q000097:blood; D000073939:Dysferlin; D004576:Electromyography / Q000379:methods; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009132:Muscles / Q000473:pathology*; D049288:Muscular Dystrophies, Limb-Girdle / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009154:Mutation / Q000235:genetics; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins; D003402:Creatine Kinase; C105884:CAPN3 protein, human; D002154:Calpain