• PMID: 16893908
• Gene Name: USP9Y
• Condition: Infertility
• Association: USP9Ys role is more likely to be that of a ?ne-tuner that improves ef?ciency, rather than a provider of an essential function of human spermatogenesis
• Mutation: Deletions in USP9Y gene. Patient 1: Hgr2 (Y*(xD,E,J,N,P)underived haplogroup, Patient 2: Hgr12 (hgr N) haplogroup.
• Population size: 1345
• Population details: 995 infertile ( 2 detected with deletions in their USP9Y gene ), 350 non spermic men
• Sex: Male
• Infertility type: Male infertility
• Associated genes: DDX3Y

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

Krausz C, Degl'Innocenti S, Nuti F, Morelli A, Felici F, Sansone M, Varriale G, Forti G.

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. FAU - Krausz, Csilla AU - Krausz C AD - Andrology Unit, Department of Clinical Physiopathology, University of Florence, Italy. c.krausz@dfc.unifi.it FAU - Degl'Innocenti, Selene AU - Degl'Innocenti S FAU - Nuti, Francesca AU - Nuti F FAU - Morelli, Annamaria AU - Morelli A FAU - Felici, Federica AU - Felici F FAU - Sansone, Mauro AU - Sansone M FAU - Varriale, Gennaro AU - Varriale G