Detection of cystic fibrosis transmembrane conductance regulator (CFTR) gene rearrangements enriches the mutation spectrum in congenital bilateral absence of the vas deferens and impacts on genetic counselling

Hum Reprod. 2007 May;22(5):1285-91. doi: 10.1093/humrep/dem024. Epub 2007 Feb 28.

Abstract

Background: Mutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene have been widely detected in infertile men with congenital bilateral absence of the vas deferens (CBAVD). Despite extensive analysis of the CFTR gene using varied screening methods, a number of cases remain unsolved and could be attributable to the presence of large gene rearrangements, as recently shown for CF patients.

Methods: We carried out a complete CFTR gene study in a group of 222 CBAVD patients with strict diagnosis criteria and without renal anomaly, and searched for rearrangements using a semi-quantitative assay in a subgroup of 61 patients.

Results: The overall mutation detection rate was 87.8%, and 82% of patients carried two mutations. Ten out of the 99 different mutations accounted for 74.6% of identified alleles. Four large rearrangements were found in patients who already carried a mild mutation: two known partial deletions (exons 17a to 18 and 22 to 23), a complete deletion and a new partial duplication (exons 11 to 13). The rearrangements accounted for 7% of the previously unknown alleles and 1% of all identified alleles.

Conclusions: Screening for rearrangements should be part of comprehensive CFTR gene studies in CBAVD patients and may have impacts on genetic counselling for the patients and their families.

MeSH terms

  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • France
  • Gene Deletion
  • Gene Rearrangement / genetics*
  • Genetic Counseling*
  • Genotype
  • Humans
  • Male
  • Mutation
  • Vas Deferens / abnormalities*

Substances

  • Cystic Fibrosis Transmembrane Conductance Regulator