Analysis of cystic fibrosis transmembrane regulator and azoospermia factor polymorphisms in infertile men in relation to other abnormalities

Abstract

The aim was to determine the prevalence of compound genetic abnormalities in patients who are carriers of cystic fibrosis transmembrane regulator (CFTR) gene polymorphism and to compare our results with similar patients reported in the literature. One hundred and nine patients were identified to be carriers of CFTR gene polymorphism. Additional genetic testing for karyotype abnormalities or Y chromosome microdeletions (YMD) was performed. Three patients (2.75%) of 109 were identified to have compound genetic abnormalities. One patient had 5T/5T while the other had 6T/6T and the third had 9T/9T. The three patients had deletions of azoospermia factor regions (AZFa+b or AZFa+b+c). There were no karyotype abnormalities identified in our database. In the literature, four patients with compound CFTR mutations and YMD were identified, in three patients had karyotype abnormalities. In conclusion, compound genetic abnormalities in CFTR mutation patients can be a contributing factor when abnormal spermatogenesis is encountered.

CFTR Deletion in Mouse Testis Induces VDAC1 Mediated Inflammatory Pathway Critical for Spermatogenesis

“…It is well established that Caucasians are more likely to develop classic CFTR disease and show a higher mutation rate, such as 508 mutation, compared with Chinese and other east Asian populations [ 3 ]. A recent study showed that the 5T haplotype is relatively more common compared with fertile controls, indicating that same mutation of CFTR may be shared with different ethnicities [ 6 , 9 , 35 , 36 ]. Several studies have shown that IVF patients have more 5T mutations; therefore it has been recommended that a CFTR mutation screen should be conducted in IVF clinics as routine practice.…”

“…Our previous study and others have found that CFTR is expressed in mouse and human sperm and play important roles in sperm capacitation, however, whether CFTR dysfunction is related to spermatogenesis defects is still unclear [ 3 – 5 ]. European studies have shown that azoospermia patients have significantly higher 5T mutations compared with oligospermia patients, suggesting CFTR mutations could be related to defective spermatogenesis in humans [ 6 , 7 ]. On the other hand it is known that people from east Asia have a very low incidence of the CFTR mutation related to classic CF disease [ 8 ].…”