Analysis of mutations in the cystic fibrosis transmembrane regulator (CFTR) gene in patients with obstructive azoospermia

Bernardino, Andrea L. F.; Lima, Cintia E.; Zatz, Mayana

doi:10.1590/s1415-47572003000100001

Cited by 10 publications

(6 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Notably, the allele frequency of p. Phe508del mutation in our population is similar to that of France (4) and Spain (5). The 5T allele in our population was found with an allele frequency of 28% is very similar to that of Canada, Brazil (42,43).…”

Section: Spectrum Of Mutations Identified In Cavd Patientssupporting

confidence: 80%

Molecular and Functional Basis of Cystic Fibrosis in Indian Patients: Genetic, Diagnostic and Therapeutic Implications

Prasad

2018

Annals of the National Academy of Medical Sciences (India)

View full text Add to dashboard Cite

Cystic fibrosis (CF, MIM#219700) is a common autosomal recessive disorder among Caucasians, which was considered as rare disease for Indian population. CF is caused due to presence of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In this study, we established a spectrum of mutations from both classical CF as well as from infertile male patients with congenital absence of vas deferens (CAVD). In Indian classical CF patients, we reported 14 previously known and eight novel mutations, viz. 3986-3987 delC, 876-6 del4, 1792 InsA, L69H, S158N, Q493L, 1530L and E1329Q. The frequency of delta 508 was found to be 27%. Absolute linkage between delta 508 and KM19-GATT TUB9-M470V-T854T haplotype predicts a relatively recent appearance of delta 508 mutations in Indian population. The CFTR gene analysis in CAVD infertile males documented 13 different CFTR gene mutations and 1 intronic variant that led to aberrant splicing. P.Phe 508 del (n= 16) and p.Arg 117 His (n=4) were among the common severe forms of CFTR mutations identified. The IVS-8-T5 allele (mild form of mutations) was formed with an allele frequency of 28.3%. Eight novel mutations were also found in the CFTR gene from our patient cohort. We also investigated whether genetic modifiers, viz. transforming growth factor (TGF-β) and endothelial receptor type A (EDNRA) of CF lung disease also predispose to CAVD in association with CFTR mutations, which were associated with the CAVD phenotype.Functional characterization of identified 11 novel CFTR gene mutations disclosed that a significant reduction in channel activity for L69H and S549N mutants in CFTR expressing cells was observed whereas impaired CFTR protein maturation was noticed only in L69H substitute CFTR. CFTR correctors (VX809) rescued the defect due to L69H mutation, which is evidenced from detection of C band in L69H mutant expressing cells pre-treated with VX809. The chloride channel activity in S549N and L69H mutant CFTR was also restored in presence of CFTR potentiators VX770.Above findings confirms heterogeneity of CFTR mutations in Indian classical and non-classical CF patients. They may help in developing a strategy to develop counseling and therapeutic approach for CF patients in India.

show abstract

Section: Spectrum Of Mutations Identified In Cavd Patientssupporting

confidence: 80%

Molecular and Functional Basis of Cystic Fibrosis in Indian Patients: Genetic, Diagnostic and Therapeutic Implications

Prasad

2018

Annals of the National Academy of Medical Sciences (India)

View full text Add to dashboard Cite

show abstract

“…Bernardino et al (2003) in a study with 20 Brazilian patients (17 with CBAVD and 3 with another type of obstructive azoospermia) found a frequency of the IVS9-5T allele in 23.5% of the men with CBAVD, similar to the one found in other studies (Chillón et al , 1995; Casals et al , 2000), which points out its relation with the CBAVD phenotype. Although individuals with an IVS9-5T allele in trans with a severe mutation in the CFTR gene show fertility problems (CBAVD) or other atypical forms of CF, approximately 40% are healthy and fertile due to the incomplete penetrance of this allele (Chillón et al , 1995; Zielenski et al , 1995).…”

Section: Introductionsupporting

confidence: 81%

Congenital bilateral absence of the vas deferens as an atypical form of cystic fibrosis: reproductive implications and genetic counseling

et al. 2017

View full text Add to dashboard Cite

Congenital bilateral absence of the vas deferens (CBAVD) is found in 1% to 2% of males with infertility and is present in 6% of obstructive azoospermia cases. Nearly 95% of men with cystic fibrosis (CF, an autosomal recessive disorder) have CBAVD. There are genetic links between CBAVD and CF. Some mutations in the gene encoding cystic fibrosis transmembrane conductance regulator (CFTR) can lead to CBAVD as a monosymptomatic form of CF. With the use of assisted reproductive techniques (ART), especially testicular or epididymal sperm aspiration, intracytoplasmic sperm injection, and in vitro fertilization, it is possible that men with CBAVD can produce offspring. Therefore, genetic counseling should be offered to couples undergoing ART to discuss the probability of having offspring that carry CFTR gene mutations. The aim of this review was to present the main cause of CBAVD, to call attention to its implications for assisted reproduction, and to show the importance of genetic counseling for couples where men have CBAVD, as they can have offspring with a lethal disease.

show abstract

“…The articles included in this revision also mentioned infertility caused by anatomic factors, such as the congenital bilateral absence of the deferential duct, an anomaly responsible for approximately 6% of the cases of obstructive azoospermia, and for 1-2% of the cases of infertility in men ( Bernardino et al ., 2003 ).…”

Section: Discussionmentioning

confidence: 99%

Factors related to infertility in Brazil and their relationship with success rates after assisted reproduction treatment: an integrative review

Maranhão

Mariz

Araújo

et al. 2020

JBRA

View full text Add to dashboard Cite

This integrative review evaluated the most commonly diagnosed causes of infertility in men and women in Brazil, as well as the medically assisted reproduction technologies regularly employed in these cases. We searched in four electronic databases (PubMed, including Medline; Scopus; Web of Science and LILACS), and two grey literature (Google Scholar and OpenGrey), guided by the focused question: "What are the main factors responsible for male and female infertility in Brazil, and what are its relationships with success rates after assisted reproduction treatment?". We included interventional or observational studies, without limitation by language or year of publication. Our searches in the electronic indexers recovered 1,119 articles, and after analyzing the inclusion and exclusion criteria, 27 articles composed the body of analysis for this review. We grouped the studies into four themes: factors responsible for male and female infertility, assisted reproductive technologies (ART) used in the infertility treatment, assisted reproduction procedures, and clinical predictors of success rates in ART. Despite the scarcity of studies analyzing the association between infertility and assisted reproductive technologies in Brazil, it was possible to infer that the most prevalent infertility cause in women was endometriosis, while in men it was azoospermia. The most widely assisted reproductive technology applied in the country is the intracytoplasmic injection of spermatozoa (ICSI), ensuring better success rates in the treatment of infertility for men and women.

show abstract

Analysis of mutations in the cystic fibrosis transmembrane regulator (CFTR) gene in patients with obstructive azoospermia

Cited by 10 publications

References 13 publications

Molecular and Functional Basis of Cystic Fibrosis in Indian Patients: Genetic, Diagnostic and Therapeutic Implications

Molecular and Functional Basis of Cystic Fibrosis in Indian Patients: Genetic, Diagnostic and Therapeutic Implications

Congenital bilateral absence of the vas deferens as an atypical form of cystic fibrosis: reproductive implications and genetic counseling

Factors related to infertility in Brazil and their relationship with success rates after assisted reproduction treatment: an integrative review

Contact Info

Product

Resources

About