The relationship between common mutations in CFTR, AR genes, Y chromosome microdeletions and karyotyping abnormalities with very severe oligozoospermia in Iranian men.

BACKGROUND: Male infertility due to very severe oligozoospermia has been associated with some genetic risk factors. OBJECTIVE: To investigate the distribution of the mutations in the CFTR gene, the CAG-repeat expansion of the AR gene, also Y chromosome microdeletions and karyotyping abnormalities in very severe oligozoospermia patients. METHODS: In the present case-control study, 200 patients and 200 fertile males were enrolled. All patients and control group were karyotyped. Microdeletions were evaluated using multiplex PCR. Five common CFTR mutations were genotyped using the ARMS-PCR technique. The CAG-repeat expansion in the AR gene was evaluated for each individual using sequencing. RESULTS: Overall 4% of cases shows a numerical and structural abnormality. 7.5% of patients had a deletion in one of the AZF regions on Yq, and 3.5% had a deletion in two regions. F508del was the most common (4.5%) CFTR gene mutation; G542X, and W1282X were detected with 1.5% and 1% respectively. One patient was found to have AZFa microdeletion and F508del in heterozygote form; one patient had AZFb microdeletion with F508del. F508del was seen as compound heterozygous with G542X in one patient and with W1282X in the other patient. The difference in the mean of the CAG-repeats in the AR gene in patients and control groups was statistically significant (P = 0.04). CONCLUSION: Our study shows the genetic mutations in men with severe oligozoospermia and given the possibility of transmission of these disorders to the next generation by fertilization, counseling and genetic testing are suggested for these couples before considering ICSI.

The prevalence of common CFTR gene mutations and polymorphisms in infertile Iranian men with very severe oligozoospermia.

Due to progress in infertility etiology, several genetic bases of infertility are revealed today. This study aimed to investigate the distribution of mutations in the CFTR gene, M470V polymorphism, and IVS8 poly T. Furthermore, we aimed to examine the hotspot exons (4, 7, 9, 10, 11, 20, and 21 exons) to find a new mutation in cystic fibrosis transmembrane conductance regulator (CFTR) gene among infertile Iranian men very severe oligozoospermia (<1 million sperm/mL ejaculate fluid). In the present case-control study, 200 very severe oligozoospermia (20-60s) and 200 fertile men (18-65s) were registered. Five common CFTR mutations were genotyped using the ARMS-PCR technique. The M470V polymorphism was checked out by real-time PCR, and poly T and exons were sequenced. The F508del was the most common (4.5%) CFTR gene mutation; G542X and W1282X were detected with 1.5% and 1%, respectively. N1303K and R117H were detected in 0.5% of cases. F508del was seen as a heterozygous compound with G542X in one patient and with W1282X in the other patient. Also, in the case of M470V polymorphism, there are differences between the case and control groups (p=0.013). Poly T assay showed statistical differences in some genotypes. The study showed no new mutation in the exons mentioned above. Our results shed light on the genetic basis of men with very severe oligozoospermia in the Iranian population, which will support therapy decisions among infertile men.

The prevalence of common CFTR mutations in Iranian infertile men with non-CAVD obstructive azoospermia by using ARMS PCR techniques.

PURPOSE: To evaluate five common cystic fibrosis trans-membrane conductance regulator (CFTR) mutations (ΔF508, G542X, R117H, W1282X and N1303K) in the Iranian infertile men with noncongenital absence of vas deferens (CAVD) obstructive azoospermia. METHODS: The common CFTR gene mutations were tested on blood samples from 53 infertile men with non-CAVD obstructive azoospermia and 50 normal men as control individuals. Genomic DNA is extracted from the whole blood and the common CFTR mutations have been detected by the amplification refractory mutation system (ARMS) techniques. RESULTS: The common CFTR mutations were found positive in 5/53)9.43%(for ΔF508 and 4/53)7.55%(for G542X mutation of all patients tested. Also, no CFTR mutations were detected in the normal men. CONCLUSION: The common CFTR mutations were detected in 9/53(17%) infertile men with non-CAVD obstructive azoospermia. Pre-treatment CFTR mutation analysis remains critical to distinguish cystic fibrosis (CF) genotypes for men with non CAVD obstructive azoospermia.