Cystic Fibrosis Transmembrane Conductance Regulator Gene Variations in Coding and Noncoding Regions in Congenital Bilateral Absence of the Vas Deferens Dependent Infertility

Abstract

Cystic fibrosis is the most common monogenic autosomal recessive inherited severe disease with 1/25 carrier frequency and 1/2500 occurrence rate in Caucasian. It is a systemic disease caused by variations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) epithelial chloride channel gene. Because this transmembrane protein exists in all mucous and secretory epithelia, all mucosa lining organs are affected from genetic variations that produce a defective protein, primarily lungs, pancreas, intestine, vasa deferens etc. It is known that, male infertility based on congenitally bilateral absence of the vas deferens (CBAVD), is caused in more than 70 percent by CFTR gene variations. In our study we analysed gene variations in 22 CBAVD patients by screening and DNA sequencing of the whole coding regions, 5’ UTR and exon-intron boundaries of CFTR gene. Hundred percent of the patients showed at least one and about 91% two or more CFTR gene variations. Although only 31.8% revealed known disease producing variations in the coding regions, 2 of 22 patients (9%) showed only one, 10 of them (45.45%) had two and 10 patients (45.45%) yielded 3 to 5 genetic variations in CFTR gene coding region, in the noncoding 5’UTR or at the exon-intron boundaries. Intron 6a, 8, 14a and exon 10 of CFTR gene are highly variable and polymorphic in CBAVD patients. In conclusion, CFTR gene variations in coding and noncoding regions, might be the main and only cause in CBAVD patients.