title: Heterogenous spectrum of CFTR gene mutations in Indian patients with congenital absence of vas deferens.
abstract: BACKGROUND
  Mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene can cause congenital bilateral absence of vas deferens. Yet, the spectrum and frequency of CFTR mutations in Indian males with congenital absence of vas deferens (CAVD) is unknown.
  
  
  METHODS
  We investigated 50 Indian males, diagnosed with unilateral or bilateral absence of vas deferens at the PGIMER, Chandigarh, for the presence of the most common CFTR gene mutations as well as unknown mutations by single-strand conformation polymorphism followed by sequence analysis.
  
  
  RESULTS
  This study led to the identification of 12 CFTR gene mutations on 48% of 100 Indian CAVD chromosomes. CFTR mutations were identified on both alleles in 11 patients (22%) and on one allele in 26 patients (52%). Novel CFTR mutations identified were L69H, F87I, G126S, F157C, E543A, Y852F and D1270E. The T5 allele (25%) and F508del (11%) were the most common mutations identified. The most common intragenic marker haplotype for F508del was 2111 (GATT, TUB9, M470V and T854T). No mutations could be detected in 13 CAVD patients (26%), including 4 with renal malformations.
  
  
  CONCLUSIONS
  This study confirms the molecular heterogeneity of CFTR mutations in CAVD. Although the mutation detection rate is indeed lower in Indian CAVD patients, 74% of the patients tested had at least one CFTR mutation. CAVD alleles with no mutations suggest that other changes may be located at the non-screened sites that require extensive search by direct sequencing. Furthermore, the novel CFTR mutations identified require functional studies in a cell-based system.
authors.affiliation: Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: N
authors.initials: N
authors.lastname: Sharma
authors.forename: N
authors.initials: N
authors.lastname: Acharya
authors.forename: S K
authors.initials: SK
authors.lastname: Singh
authors.forename: M
authors.initials: M
authors.lastname: Singh
authors.forename: U
authors.initials: U
authors.lastname: Sharma
authors.forename: R
authors.initials: R
authors.lastname: Prasad
mesh_terms: D000595:Amino Acid Sequence; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007194:India; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D016415:Sequence Alignment; D014564:Urogenital Abnormalities / Q000235:genetics; D014649:Vas Deferens / Q000002:abnormalities* / Q000473:pathology
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator