Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes male infertility |
| |
Authors: | 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 |
| |
Institution: | Centre Hospitalier Universitaire (CHU) de Grenoble, Département de Génétique et Procréation, Unite Fonctionelle (UF) de biochimie génétique et moléculaire, F-38700 La Tronche, France. |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|