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
Centre Hospitalier Universitaire (CHU) de Grenoble, Département de Génétique et Procréation, Unite Fonctionelle (UF) de biochimie génétique et moléculaire, F-38700 La Tronche, France.
Nat Genet. 2007 May;39(5):661-5. doi: 10.1038/ng2027. Epub 2007 Apr 15.
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.
世界卫生组织保守估计，全球有8000万人患有不孕症。男性因素被认为在所有不孕症病例中占20%-50%，但Y染色体微缺失是唯一反复报道的改变人类精子发生的遗传缺陷。我们的研究工作聚焦于体细胞染色体核型正常但精子具有典型特征（主要表现为头部较大、尾部数量不一且染色体含量增加，OMIM 243060）的不育男性。我们对十名呈现这种特征性表型的不育男性进行了全基因组微卫星扫描。在所有这些男性中，我们鉴定出一个纯合子共区域，该区域包含极光激酶C基因（AURKC），且AURKC编码序列中有一个单核苷酸缺失。此外，我们发现这种奠基者突变导致翻译提前终止，产生一种缺乏激酶结构域的截短蛋白。我们得出结论，AURKC的缺失由于产生大头多鞭毛多倍体精子而导致男性不育。
