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.
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.
Ratbi
Ilham
I
Service de Biochimie et Génétique Moléculaire, AP-HP et INSERM U841, IMRB, eq 21, Hôpital Henri-Mondor, Créteil, France.
Legendre
Marie
M
Niel
Florence
F
Martin
Josiane
J
Soufir
Jean-Claude
JC
Izard
Vincent
V
Costes
Bruno
B
Costa
Catherine
C
Goossens
Michel
M
Girodon
Emmanuelle
E
D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005602:France; D017353:Gene Deletion; D015321:Gene Rearrangement / Q000235:genetics*; D005817:Genetic Counseling; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D014649:Vas Deferens / Q000002:abnormalities*
D019005:Cystic Fibrosis Transmembrane Conductance Regulator