title: Limb-girdle muscular dystrophy in the Agarwals: Utility of founder mutations in CAPN3 gene.
abstract: OBJECTIVE
  Diagnostic evaluation of limb-girdle muscular dystrophy type 2A (LGMD2A) involves specialized studies on muscle biopsy and mutation analysis. Mutation screening is the gold standard for diagnosis but is difficult as the gene is large and multiple mutations are known. This study evaluates the utility of two known founder mutations as a first-line diagnostic test for LGMD2A in the Agarwals.
  
  
  METHODS
  The Agarwals with limb-girdle muscular dystrophy (LGMD) phenotype were analyzed for two founder alleles (intron 18/exon 19 c.2051-1G>T and exon 22 c.2338G>C). Asymptomatic first-degree relatives of patients with genetically confirmed mutations and desirous of counseling were screened for founder mutations.
  
  
  RESULTS
  Founder alleles were detected in 26 out of 29 subjects with LGMD phenotype (89%). The most common genotype observed was homozygous for exon 22 c.2338 G>C mutation followed by compound heterozygosity. Single founder allele was identified in two. Single allele was detected in two of the five asymptomatic relatives.
  
  
  CONCLUSIONS
  Eighty-nine percent of the Agarwals having LGMD phenotype have LGMD2A resulting from founder mutations. Founder allele analysis can be utilized as the initial noninvasive diagnostic step for index cases, carrier detection, and counseling.
authors.affiliation: Department of Neurology, Grant Medical College and Sir J. J. Group of Hospitals, Mumbai, Maharashtra, India.
authors.forename: Satish V
authors.initials: SV
authors.lastname: Khadilkar
authors.affiliation: Department of Neurology, Grant Medical College and Sir J. J. Group of Hospitals, Mumbai, Maharashtra, India.
authors.forename: Chetan R
authors.initials: CR
authors.lastname: Chaudhari
authors.affiliation: Centre for Advanced Molecular Diagnostics in Neuromuscular Disorders (CAMDND), Mumbai, Maharashtra, India.
authors.forename: Rashna S
authors.initials: RS
authors.lastname: Dastur
authors.affiliation: Centre for Advanced Molecular Diagnostics in Neuromuscular Disorders (CAMDND), Mumbai, Maharashtra, India.
authors.forename: Pradnya S
authors.initials: PS
authors.lastname: Gaitonde
authors.affiliation: Department of Neurology, Grant Medical College and Sir J. J. Group of Hospitals, Mumbai, Maharashtra, India.
authors.forename: Jayendra G
authors.initials: JG
authors.lastname: Yadav
keywords: Agarwal; calpainopathy; founder mutation