Journal Article

Natural transmission of USP9Y gene mutations: a new perspective on the role of AZFa genes in male fertility

Csilla Krausz, Selene Degl'Innocenti, Francesca Nuti, Annamaria Morelli, Federica Felici, Mauro Sansone, Gennaro Varriale and Gianni Forti

in Human Molecular Genetics

Volume 15, issue 18, pages 2673-2681
Published in print September 2006 | ISSN: 0964-6906
Published online August 2006 | e-ISSN: 1460-2083 | DOI:
Natural transmission of USP9Y gene mutations: a new perspective on the role of AZFa genes in male fertility

Show Summary Details


Deletions of the azoospermia factor (AZF) regions of the Y chromosome are associated with severe spermatogenic failure and represent the most frequent molecular genetic cause of azoospermia and severe oligozoospermia. The exact role of the candidate AZF genes is largely unknown due to both the extreme rarity of naturally occurring AZF gene-specific mutations and the lack of functional assays. Here, we report the fine characterization of two different deletions in the USP9Y gene (one of the two candidate genes in the AZFa region), which have been transmitted through natural conception in two unrelated families. The associated mild testicular phenotype, in both cases, is in sharp contrast with that of the two previously reported infertile patients bearing a mutation of the same gene. In conclusion, to date, the USP9Y gene has been considered as one of the major Y-linked spermatogenesis genes, based on both its position within the AZFa region and previous reports that correlated USP9Y mutation to severe spermatogenic failure and infertility. This view is now substantially changed because our findings clearly demonstrate that during human spermatogenesis, USP9Y is more likely a fine tuner that improves efficiency, rather than a provider of an essential function. More importantly, the observed natural conceptions suggest that the protein is not required for the final sperm maturation process or for the acquisition of sperm fertilizing ability, providing a new perspective on the role played by the USP9Y gene in male fertility.

Journal Article.  4673 words.  Illustrated.

Subjects: Genetics and Genomics

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