Mutations in the Cystic Fibrosis Gene in Patients with Congenital Absence of the Vas Deferens

Abstract

Background. Congenital bilateral absence of the vas deferens (CBAVD) is a form of male infertility in which mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been identified. The molecular basis of CBAVD is not completely understood. Although patients with cystic fibrosis have mutations in both copies of the CFTR gene, most patients with CBAVD have mutations in only one copy of the gene.Methods. To investigate CBAVD at the molecular level, we have characterized the mutations in the CFTR gene in 102 patients with this condition. None had clinical manifestations of cystic fibrosis. We also analyzed a DNA variant (the 5T allele) in a noncoding region of CFTR that causes reduced levels of the normal CFTR protein. Parents of patients with cystic fibrosis, patients with types of infertility other than CBAVD, and normal subjects were studied as controls.Results. Nineteen of the 102 patients with CBAVD had mutations in both copies of the CFTR gene, and none of them had the 5T allele. Fifty-four patients had a mutation in one copy of CFTR, and 34 of them (63 percent) had the 5T allele in the other CFTR gene. In 29 patients no CFTR mutations were found, but 7 of them (24 percent) had the 5T allele. In contrast, the frequency of this allele in the general population was about 5 percent.Conclusions. Most patients with CBAVD have mutations in the CFTR gene. The combination of the 5T allele in one copy of the CFTR gene with a cystic fibrosis mutation in the other copy is the most common cause of CBAVD. The 5T allele mutation has a wide range of clinical presentations, occurring in patients with CBAVD or moderate forms of cystic fibrosis and in fertile men. (N Engl

A multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART)

“…Additional mutations include the 5 T polymorphism within intron 8 in the CFTR gene that was found in 21 % of the subjects and is considered a mild mutation, specifically associated with male sterility [43,80]. The 7 T polymorphism within intron 8 and the missense R117H mutation within exon 4 in the CFTR gene were also reported [4,81]. Other common mutations including G542X, G551D, R553X, W1282X and N1303K occur with a frequency of 1-2 %.…”

The CFTR polymorphisms poly-T, TG-repeats and M470V in Chinese males with congenital bilateral absence of the vas deferens

“…The 5T variant in the intron 8 polythymidine tract was the most frequent CFTR gene alteration identified in Caucasian individuals with CBAVD. 23 This nonfunctional CFTR mRNA accounts for up to 92% of the total mRNA when the 5T allele is found on both CFTR genes. 11 We observed a significant proportion of Chinese CBAVD males who have the 5T allele (44.50%), as compared with the control males (13.46%).…”

Malnutrition in adults with cystic fibrosis

“…Chronic bronchial colonization with Pseudomonas aeruginosa, meconium ileus, distal intestinal obstruction syndrome (DIOS), diabetes mellitus, cirrhosis, gallstones and gastroesophageal reflux were recorded. The CFTR gene was first analyzed by using a commercial kit based on oligonucleotide ligation assay then, if negative, screened by specific methods (Highsmith et al, 1994;Bienvenu et al, 1995;Chillon et al, 1995). CFTR genotypes were classified based on the primary mechanism of defective CFTR function (Welsh & Smith, 1993;Zielenski & Tsui, 1995) into three groups (mild, severe or indeterminate CFTR genotype) according to the probable effect of their mutations on CFTR function, regardless of clinical severity.…”