Screening by single-molecule molecular inversion probes targeted sequencing panel of candidate genes of infertility in azoospermic infertile Jordanian males

Abstract

Infertility is a common health problem that affects around 1 in 6 couples in the United States, where half of these cases are attributed to male factors. Genetics play an important role in infertility and it is estimated that up to 50% of cases are due to genetic factors. Despite this, many male infertility cases are still idiopathic. This study aimed to identify the presence of possibly pathogenic rare variants in a set of candidate genes related to azoospermia in 69 Jordanian men using a next-generation sequencing-based panel covering more than a hundred male infertility related genes. A total of 9 variants were found and validated. Among them, two variants included reported pathogenic variants in CFTR and one novel pathogenic variant in the USP9Y gene. We also report the detection of 6 other variants with uncertain significance in other genes. Interestingly, male cases with CFTR variants did not show the expected cystic fibrosis phenotypes except for infertility. This work helps to uncover the contribution of additional genetic factors to the aetiology of male infertility and highlights the importance to obtain more reliable information about the presence of genetic variation in the Jordanian population.

Keywords:

• Male infertility
• Azoospermia
• single-molecule Molecular Inversion Probes
• next generation sequencing
• CFTR mutations

Acknowledgements

The authors thank all volunteers who participated in this study. Many thanks to the Royal Medical services for approving and participating in the study.

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This study was funded by the deanship of research at Jordan University of science and technology [Grant # 12/2019]. J. A. V. is supported by grants from The Netherlands Organization for Scientific Research [918-15-667] as well as an Investigator Award in Science from the Wellcome Trust [209451].