Cystic fibrosis Δf508 mutation screening in Brazilian women with altered fertility

Abstract

Cystic Fibrosis (CF) is an autosomal recessive disease, caused by mutations in the Cystic Fibrosis Transmembrane Regulator gene (CFTR). The most frequent mutation in CF is ΔF508. The disease is clinically characterized by elevated concentrations of sweat chlorides and abnormally thick mucus. It affects organs such as lung, pancreas, gastrointestinal and reproductive tract. Women with CF commonly present delayed puberty and amenorrhea due to malnutrition. Our objective was to screen the presence of ΔF508 mutation in 24 women with altered fertility. Nine of these women presented reduced fertility without a known cause, four showed polycystic ovaries and two had early menopause. One woman with early menopause was a carrier of the ΔF508 mutation. Our study demonstrates that it is possible that the frequency of CF mutations among patients with altered fertility may be higher than expected. Previous data showed that fibrocystic women can show reduced fertility, maternal mortality associated with pregnancy and increased incidence of spontaneous abortion. We therefore recommend that women with reduced fertility undertake genetic tests for a better evaluation of pregnancy risks and clinical monitoring.

Expanded carrier screening for preconception reproductive risk assessment: Prevalence of carrier status in a Mexican population

“…Furthermore, CFTR variants were more commonly detected in males compared with females, even though the difference did not reach statistical significance ( P = .46). The CF carrier status within our study was consistent with prior published reports of CF carrier prevalence on infertile male and females . The overall CF prevalence in our population is higher than the prevalence showed by Sugarman et al who found a 2.3% CFTR carrier frequency in Hispanic populations, although the population analyzed in that study consisted a broad U.S. based Hispanic residents and did not assess native Mexican Hispanics .…”

Female cystic fibrosis mutation carriers and assisted reproductive technology: does carrier status affect reproductive outcomes?

“…In 2011, Brunoro et al observed a higher percentage of CF carriers than expected among the 24 women with altered fertility in their study cohort (40). Another study in 2011 by Tomaiuolo et al showed an increased frequency of a specific CF mutation-the 5T haplotype-among women with tubal disease (32).…”

More evidence for widespread antagonistic pleiotropy in polymorphic disease alleles

“…Cystic fibrosis (CF) is an autosomal recessive disorder caused by various mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, but the ΔF508 mutation (a deletion of the phenylalanine at amino acid position 508 in the protein) accounts for 70% of CF patients ( Kerem et al, 1989 ). Mutations in the CFTR gene encode a nonfunctional chloride channel, causing a broad range of deleterious effects ( Ramananda et al, 2024 ) including obstructive lung disease and increased susceptibility to respiratory infections ( Rowntree and Harris, 2003 ), pancreatic disorders ( Estivill et al, 1995 ), and reduced fertility in both males ( Alves et al, 2015 ) and females ( Brunoro et al, 2011 ).…”