Cystic fibrosis transmembrane conductance regulator (CFTR) gene abnormalities in Indian males with congenital bilateral absence of vas deferens & renal anomalies.

Background & objectives: The role of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in congenital bilateral absence of vas deferens and unilateral renal agenesis (CBAVD-URA) has been controversial. Here, we report the cases of five Indian males with CBAVD-URA. The objective was to evaluate the presence or absence of CFTR gene mutations and variants in CBAVD-URA. The female partners of these males were also screened for cystic fibrosis (CF) carrier status. Methods: Direct DNA sequencing of CFTR gene was carried out in five Indian infertile males having CBAVD-URA. Female partners (n=5) and healthy controls (n=32) were also screened. Results: Three potential regulatory CFTR gene variants (c.1540A>G, c.2694T>G and c.4521G>A) were detected along with IVS8-5T mutation in three infertile males with CBAVD-URA. Five novel CFTR gene variants (c.621+91A>G, c.2752+106A>T, c.2751+85_88delTA, c.3120+529InsC and c.4375-69C>T), four potential regulatory CFTR gene variants (M470V, T854T, P1290P, Q1463Q) and seven previously reported CFTR gene variants (c.196+12T>C, c.875+40A>G, c.3041-71G>C, c.3271+42A>T, c.3272-93T>C, c.3500-140A>C and c.3601-65C>A) were detected in infertile men having CBAVD and renal anomalies Interpretation & conclusions: Based on our findings, we speculate that CBAVD-URA may also be attributed to CFTR gene mutations and can be considered as CFTR-related disorder (CFTR-RD). The CFTR gene mutation screening may be offered to CBAVD-URA men and their female partners undergoing ICSI. Further studies need to be done in a large sample to confirm the findings.

CFTR gene mutation in patients with congenital bilateral absence of vas deferens / 中华泌尿外科杂志

Objective To study the frequency of cystic fibrosis transmembrane conductance regulator(CFTR)mutations in patients with congenital bilateral absence of vas deferens(CBAVD).Methods Eighty-five CBAVD patients were collected from May 2007 to May 2009.The diagnosis of CBAVD included azoospermia,normal of 4 sex hormone items,absence of seminal vesicle,normal volume of testicular and epididymis dilated siltation.And 85 normal fertile men served as controls.Genomic DNA was isolated from peripheral blood.The mutations of CFTR exons 10,11 were detected by PCR-single strand conformation polymorphism,and direct sequencing was performed on 85 cases of CBAVD and the control males.Results Of the 85 CBAVD,10 cases(11.8％)exhibited an abnormal CFTR gene mutation,with 4 cases I556V,2 cases M469V,and 1 case of E527N,A F508,L558S,S485C.No mutations were detected in 85 controls.There was a significant difference between the 2 groups(x2 =8.606,P =0.003).Conclusions CBAVD might be caused by the CFTR mutations.The frequencies and the spectrum of CFTR mutations might be different from those Caucasian population in the west country.