The Spectrum of Common Mutations in CFTR, AR Gene, and the Y Chromosome Microdeletions and Karyotyping Abnormalities in Phenotypic Male with Very Severe Oligozoospermia

Abstract Male infertility due to very severe oligozoospermia has been associated with a number of genetic risk factors.This association in patients with sperm concentration lower than 1× 106 ml are not yet fully studied.The present study aims to investigate the distribution of the mutations in the CFTR gene, the CAG repeat expansion of the AR gene as well as Y chromosome microdeletions and karyotyping abnormalities in very severe oligozoospermia patients from the Iranian population. In the present case-control study 200 severe oligozoospermia and 200 fertile males were enrolled. All patients karyotyped for diagnosis of the chromosomal abnormalities using routine. 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 the number of repeats in each patient using sequencing. Overall, 4% of cases have 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 repeat in the AR gene in patients and controls were statistically significant (P = 0.04). Our study shows that ICSI in couples with very severe oligozoospermia can lead to an increase in children who are at risk of unbalanced chromosomal complement, male infertility due to transmission of Y-chromosomal microdeletion , AR- CAG repeat and cystic fibrosis if both partners carry the CFTR gene mutation. Genetic testing and counseling before considering ICSI is suggested for these couples.