Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes male infertility.

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Dieterich, Klaus | Soto Rifo, Ricardo | Faure, Anne Karen | Hennebicq, Sylviane | Ben Amar, Baha | Zahi, Mohamed | Perrin, Julia | Martinez, Delphine | Sèle, Bernard | Jouk, Pierre-Simon | Ohlmann, Théophile | Rousseaux, Sophie | Lunardi, Joel | Ray, Pierre, F.

Edité par CCSD ; Nature Publishing Group -

International audience. The World Health Organization conservatively estimates that 80 million people suffer from infertility worldwide. Male factors are believed to be responsible for 20-50% of all infertility cases, but microdeletions of the Y chromosome are the only genetic defects altering human spermatogenesis that have been reported repeatedly. We focused our work on infertile men with a normal somatic karyotype but typical spermatozoa mainly characterized by large heads, a variable number of tails and an increased chromosomal content (OMIM 243060). We performed a genome-wide microsatellite scan on ten infertile men presenting this characteristic phenotype. In all of these men, we identified a common region of homozygosity harboring the aurora kinase C gene (AURKC) with a single nucleotide deletion in the AURKC coding sequence. In addition, we show that this founder mutation results in premature termination of translation, yielding a truncated protein that lacks the kinase domain. We conclude that the absence of AURKC causes male infertility owing to the production of large-headed multiflagellar polyploid spermatozoa.

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