Novel cause of hereditary obstructive azoospermia: a T2 allele in the CFTR gene

Reprod Biomed Online. 2009 Mar;18(3):327-32. doi: 10.1016/s1472-6483(10)60089-2.

Abstract

Congenital bilateral absence of the vas deferens (CBAVD) is a frequent cause of obstructive azoospermia, and caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. A novel TG(13)T(2) allele was identified in a CBAVD patient with no clinical cystic fibrosis phenotype, normal pancreatic function, normal sweat chloride concentrations and no Y chromosome microdeletions. This case was studied for CFTR mutations, IVS8-poly(T), and M470V exon 10 missense polymorphism. One novel allele was detected in the (TG)(m)(T)(n) loci that had not been reported previously. This patient carried a [TG(11)T(9); R117H; p.Met470Val] haplotype on the other chromosome. Since the TG(13)T(2) allele was a compound heterozygote with R117H mutation, it was difficult to judge the severity of this allele. To better understand the complex regulation of exon 9 splicing, the levels of correctly spliced CFTR transcripts in CFTR-expressing epithelial cells derived from vas deferens and epididymis were analysed. These data emphasize the role of the T2 allele in CBAVD, and identify the T2 allele as a severe CBAVD disease-causing mutation. According to the data, the longer (TG)(m) polymorphic tract increases the proportion of transcripts with exon 9 deletion (9-), but only when activated by the short T allele.

Publication types

  • Case Reports

MeSH terms

  • Alleles*
  • Amino Acid Sequence
  • Azoospermia / genetics*
  • Base Sequence
  • Computational Biology
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • DNA / genetics
  • Exons
  • Haplotypes
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation
  • RNA Splicing

Substances

  • Cystic Fibrosis Transmembrane Conductance Regulator
  • DNA