A Novel Mutation of DAX-1 Associated with Secretory Azoospermia.

Secretory azoospermia is a severe form of male infertility caused by unknown factors. DAX-1 is predominantly expressed in mammalian reproductive tissues and plays an important role in spermatogenesis because Dax-1 knockout male mice show spermatogenesis defects. To examine whether DAX-1 is involved in the pathogenesis of secretory azoospermia in humans, we sequenced all of the exons of DAX-1 in 776 patients diagnosed with secretory azoospermia and 709 proven fertile men. A number of coding mutations unique to the patient group, including two synonymous mutations and six missense mutations, were identified. Of the missense mutations, our functional assay demonstrated that the V385L mutation caused the reduced functioning of DAX-1. This novel mutation (p. V385L) of DAX-1 is the first to be identified in association with secretory azoospermia, thereby highlighting the important role of DAX-1 in spermatogenesis.

分泌性无精子症是一种由未知因素导致的男性不育的严重形式。DAX - 1主要在哺乳动物生殖组织中表达，并且在精子发生过程中起重要作用，因为Dax - 1基因敲除的雄性小鼠表现出精子发生缺陷。为了检验DAX - 1是否参与人类分泌性无精子症的发病机制，我们对776例被诊断为分泌性无精子症的患者和709例已证实具有生育能力的男性的DAX - 1所有外显子进行了测序。我们发现了一些患者组特有的编码突变，包括2个同义突变和6个错义突变。在这些错义突变中，我们的功能检测表明V385L突变导致DAX - 1功能降低。DAX - 1的这种新突变（p.V385L）是首次被发现与分泌性无精子症相关，从而突显了DAX - 1在精子发生中的重要作用。