Screening of mutations in the CFTR gene in 1195 couples entering assisted reproduction technique programs

Abstract

Genetic testing of the cystic fibrosis transmembrane conductance ( CFTR) gene is currently performed in couples undergoing assisted reproduction techniques ( ART), because of the high prevalence of healthy carriers in the population and the pathogenic relationship with congenital bilateral absence of vas deferens ( CBAVD). However, discordant data have been reported concerning the usefulness of this genetic test in couples with no family history of cystic fibrosis ( CF). In this study, we report the results of CFTR molecular screening in 1195 couples entering ART. Genetic testing was initially carried out in a single partner of each couple. CFTR mutations were detected in 55 subjects ( 4.6%), a percentage that overlaps with the one reported in the general population. However, significantly higher frequencies of were found in CBAVD individuals ( 37.5%) and in males with nonobstructive azoospermia ( 6.6%). The 5T allele was found in 78 patients ( 6.5%). This figure was again significantly different in males with nonobstructive-azoospermia ( 9.9%) and in those with CBAVD ( 100%). All together, 139 subjects ( 11.6%) had either a CFTR mutation or the 5T allele. Subsequent molecular analysis of their partners disclosed a CFTR mutation or 5T allele in nine cases ( 6.5%). However, none of these couples had CFTR alterations in both members, a CFTR mutation being invariably present in one partner and the 5T allele in the other. In order to improve genetic counselling of these couples, the TG-M470V-5T association was analyzed, and a statistically significant relationship between 12TG-V470 and CBAVD was detected

Genetic screening in 2,710 infertile candidate couples for assisted reproductive techniques: results of application of Italian guidelines for the appropriate use of genetic tests

“…Similar results were reported by the only other large study conducted, including infertile couples undergoing assisted reproduction techniques and not only oligospermic men (28). This would support the hypothesis that when screening is performed on a large population and not only on selected men, infertility does not appear to be a risk factor for a higher chance of being a carrier of CFTR mutations.…”

Cystic fibrosis detection in high-risk Egyptian children and CFTR mutation analysis

“…Although this change is described as a sequence variant based on its relative frequency (Cystic Fibrosis Mutation databasehttp://www.genet.sickkids.on.ca/ cftr/), it has been associated with clinical significance when found in combination with the 5T allele in intron eight [28]. Although our two patients were homozygous for the common 7T allele in intron eight, it is conceivable that the M470V amino acid substitution results in a minor contribution to the development of the phenotypic spectrum of CF [29][30][31]. The frequency of the M470V allele in the Egyptian population is not known.…”

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

“…However, we found a significant association between the TG12-5T-V470 haplotype and CBAVD (Table 5), in agreement with a previous report. 29 Thus, although a particular allele by itself might have no deleterious consequences, the combination of specific alleles at several polymorphic loci might lead to less functional or even insufficient CFTR protein. 15,30 In conclusion, this study indicates that the 5T allele in intron 8 of CFTR or IVS8-5T linked to either 12 or 13 TG repeats exhibit a high prevalence among the CBAVD patients tested.…”