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

Abstract

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 anomaliesInterpretation & 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.

The CFTR gene mild variants poly-T, TG repeats and M470V detection in Indian men with congenital bilateral absence of vas deferens

“…Genomic DNA was isolated from peripheral blood collected in ethylenediaminetetraacetic acid (EDTA) tubes using QIAamp ® DNA Blood Midi Kit (Qiagen Inc., Hilden, Germany). The complete intron 9 and exon 11 of the CFTR gene were amplified using genomic DNA from CBAVD men, their female partners and controls by polymerase chain reaction (PCR) using specific primers (Gajbhiye et al., ). PCR cycling condition of 35 cycles for intron 9 was as follows: 95°C for 3 min, 56°C for 1 min and 72°C for 1 min.…”

Prevalence of CBAVD in azoospermic men carrying pathogenic CFTR mutations ‐ Evaluated in a cohort of 639 non‐vasectomized azoospermic men

“…Since renal abnormalities occur less frequently in CBAVD/CUAVD patients with CFTR mutations compared to CBAVD/CUAVD patients without CFTR mutations, 22,24,40 it may be suggested that renal abnormalities coexisting with CBAVD/CUAVD in men without CFTR mutations may be due to a non‐ CFTR mechanism affecting major parts of the Wolffian ducts. In recent studies, it has been suggested that the polythymidine sequence and the numbers of TG repeats in exon 8 and the M470V polymorphism in exon 10, in addition to male reproductive ability, may also influence the risk of having renal abnormalities 43 . Furthermore, also EDNRA and TGF‐β1 gene polymorphisms seem to affect the incidence of CBAVD as well as development of the kidneys, seminal vesicles, epididymides, and ejaculatory ducts in men with azoospermia carrying CFTR mutations 7 …”

Clinical andrologists: Do we really need them in the era of ART?

“…Congenital bilateral absence of the vas deferens (CBAVD) is found in 2%–6% of infertile men and 25% of cases with OA. [ 62 ] An andrologist can clinically diagnose this condition. CBAVD is usually associated with mutations in cystic fibrosis transmembrane conductance regulator (CFTR) gene and congenital renal anomalies.…”