2. Academic Validation
  3. A genomics approach to male infertility

A genomics approach to male infertility

  • Genet Med. 2020 Dec;22(12):1967-1975. doi: 10.1038/s41436-020-0916-0.
Naif Alhathal 1,  Sateesh Maddirevula 2,  Serdar Coskun 3,  Hamed Alali # 1 4,  Mirna Assoum # 2,  Thomas Morris 3,  Hesham A Deek 3,  Soha A Hamed 3,  Shaheed Alsuhaibani 5,  Abdulmalik Mirdawi 1,  Nour Ewida 2,  Mashael Al-Qahtani 2,  Niema Ibrahim 2,  Firdous Abdulwahab 2,  Waleed Altaweel 1,  Majed J Dasouki 2 3,  Abdullah Assiri 6,  Wafa Qabbaj 7,  Fowzan S Alkuraya 8 9
Affiliations

Affiliations

  • 1 Department of Urology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
  • 2 Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
  • 3 Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center and College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
  • 4 Department of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia.
  • 5 Department of Urology, King Fahad University Hospital, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
  • 6 Comparative Medicine Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
  • 7 Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center and College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. [email protected].
  • 8 Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. [email protected].
  • 9 Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. [email protected].
  • # Contributed equally.
PMID: 32719396 DOI: 10.1038/s41436-020-0916-0
Abstract

Purpose: Male infertility remains poorly understood at the molecular level. We aimed in this study to investigate the yield of a "genomics first" approach to male infertility.

Methods: Patients with severe oligospermia and nonobstructive azoospermia were investigated using exome sequencing (ES) in parallel with the standard practice of chromosomal analysis.

Results: In 285 patients, 10.5% (n = 30) had evidence of chromosomal aberrations while nearly a quarter (n = 69; 24.2%) had a potential monogenic form of male infertility. The latter ranged from variants in genes previously reported to cause male infertility with or without other phenotypes in humans (24 patients; 8.4%) to those in novel candidate genes reported in this study (37 patients; 12.9%). The 33 candidate genes have biological links to male germ cell development including compatible mouse knockouts, and a few (TERB1 [CCDC79], PIWIL2, MAGEE2, and ZSWIM7) were found to be independently mutated in unrelated patients in our cohort. We also found that male infertility can be the sole or major phenotypic expression of a number of genes that are known to cause multisystemic manifestations in humans (n = 9 patients; 3.1%).

Conclusion: The standard approach to male infertility overlooks the significant contribution of monogenic causes to this important clinical entity.

Keywords

Y-chromosome microdeletion; azoospermia; oligospermia; reverse phenotyping.

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