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

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

doi:10.1038/ng2027

Journal articles

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

Klaus Dieterich ^{1, 2} Ricardo Soto Rifo ³ Anne Karen Faure ^{1, 2, 4} Sylviane Hennebicq ^{1, 2, 4} Baha Ben Amar ⁵ Mohamed Zahi ⁶ Julia Perrin ^{1, 2} Delphine Martinez ^{1, 2} Bernard Sèle ^{1, 2} Pierre-Simon Jouk ^{1, 2} Théophile Ohlmann ³ Sophie Rousseaux ^{1, 2} Joel Lunardi ^{1, 2} Pierre Ray ^{1, 2, *}

* Corresponding author

1 Département de Génétique et Procréation

2 Département de génétique et procréation

3 Virologie humaine

4 Biologie moléculaire et cellulaire de la différenciation

5 Centre de FIV

6 Centre privé de Fécondation in vitro

Abstract : 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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Journal articles

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Life Sciences [q-bio] / Genetics

Life Sciences [q-bio] / Genetics / Human genetics

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

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

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