A familial study of azoospermic men identifies three novel causative mutations in three new human azoospermia genes

Moran Gershoni, Ron Hauser, Leah Yogev, Ofer Lehavi, Foad Azem, Haim Yavetz, Shmuel Pietrokovski*, Sandra E. Kleiman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

107 Scopus citations


Purpose:Up to 1% of all men experience azoospermia, a condition of complete absence of sperm in the semen. The mechanisms and genes involved in spermatogenesis are mainly studied in model organisms, and their relevance to humans is unclear because human genetic studies are very scarce. Our objective was to uncover novel human mutations and genes causing azoospermia due to testicular meiotic maturation arrest.Methods:Affected and unaffected siblings from three families were subjected to whole-exome or whole-genome sequencing, followed by comprehensive bioinformatics analyses to identify mutations suspected to cause azoospermia. These likely mutations were further screened in azoospermic and normozoospermic men and in men proven to be fertile, as well as in a reference database of local populations.Results:We identified three novel likely causative mutations of azoospermia in three genes: MEIOB, TEX14, and DNAH6. These genes are associated with different meiotic processes: meiotic crossovers, daughter cell abscission, and possibly rapid prophase movements.Conclusion:The genes and pathways we identified are fundamental for delineating common causes of azoospermia originating in mutations affecting diverse meiotic processes and have great potential for accelerating approaches to diagnose, treat, and prevent infertility.

Original languageEnglish
Pages (from-to)998-1006
Number of pages9
JournalGenetics in Medicine
Issue number9
StatePublished - 1 Sep 2017


FundersFunder number
Crown Human Genome Center
Weizmann Institute of Science Kekst Family Center for Medical Genetics


    • azoospermia
    • crossover
    • meiosis
    • rapid prophase movements
    • whole-exome and whole-genome sequencing


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