Mutations of the cystic fibrosis transmembrane conductance regulator gene in males with congenital bilateral absence of the vas deferens: Reproductive implications and genetic counseling (Review)

Abstract

congenital bilateral absence of the vas deferens (cBaVd) is predominantly caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. cBaVd accounts for 2-6% of male infertility cases and up to 25% of cases of obstructive azoospermia. With the use of pre-implantation genetic diagnosis, testicular or epididymal sperm aspiration, intracytoplasmic sperm injection and in vitro fertilization, patients affected by cBaVd are able to have children who do not carry CFTR gene mutations, thereby preventing disease. Therefore, genetic counseling should be provided to couples receiving assisted reproductive techniques to discuss the impact of CFTR gene mutations on reproductive health. In the present article, the current literature concerning the CFTR gene and its association with CBAVD is reviewed. Contents 1. Introduction 2. Overview of CFTR structure and function 3. The CFTR gene and development of the vas deferens 4. The CFTR gene in patients with CBAVD 5. Hotspot mutation types in patients with CBAVD 6. Assisted reproductive techniques and genetic counselling 7. Conclusions

Mathematical models of cystic fibrosis as a systemic disease

“…Males often face an obstruction of the vas deferens, which carries sperm from the testes to the penis; the vas deferens may even be absent (Cai & Li, 2022). The obstruction is often encountered in CF (Cui et al, 2020). As a specific example, the mutation c.‐195C>A and c.‐34C>T occurs in a conserved area of the promoter region of the CFTR (Feng et al, 2019), but several other mutations have been identified.…”

A comprehensive review of cystic fibrosis in Africa and Asia

“… Ref. Country Nucleotide/“Variant cDNA name (Variant protein name) Legacy Name Kunitomo et al, 1991 , Ahn et al, 2005 , Lin et al, 2019 South Korea c.-8G>C 8G>C Norzila et al, 2005 , Iso et al, 2019 , Guo et al, 2018 Japan c.-8G>C 8G>C Wang et al, 2019 , Teeratakulpisarn et al, 2006 , Lumpaopong et al, 2009 Taiwan c.-8G>C 8G>C Ngukam et al, 2004 Indonesia c.-8G>C 8G>C/G Norzila et al, 2005 , Iso et al, 2019 , Guo et al, 2018 Japan c.-8G>C 8G>C/G Wakabayashi-Nakao et al, 2019 Iran c.1000C >T (p.Arg334Trp) R334W Izumikawa et al, 2009 Turkey c.1000C >T, p.Arg334Trp) R334W Prasad et al, 2010 , Cui et al, 2020 , Liu et al, 2015 China c.1000C >T(p.Arg334Trp) R334W Rawashdeh and Manal, 2000 Jordan c.1000C >T(p.Arg334Trp) R334W Des Georges et al, 1997 , Farra et al, 2010 Syria c.1000C >T(p.Arg334Trp) R334W Norzila et al, 2005 , Iso et al, 2019 , Guo et al, 2018 japan c.1040G>A (p.Arg347His) R347H …”

Therapeutic potential of phytochemicals for cystic fibrosis

“…Due to CBAVD, more than 90% of male patients with CF are infertile. 17 To diagnose CF patients, the following criteria should be evaluated; positive sweat chloride test, clinical symptom(s) of the disease consistent with CF in at least one organ, and presence of at least two pathogenic variants in the CFTR gene in different alleles. 18,19 According to the latest guidelines, a sweat chloride level ≥ 60 mmol/L suggests a likelihood that CF is present, whereas a sweat chloride level under 30 mmol/L suggests that CF is unlikely.…”

“…Also, congenital bilateral absence of the vas deferens (CBAVD) is one of the effects of CF on the male reproductive system. Due to CBAVD, more than 90% of male patients with CF are infertile 17 …”