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

Lisha Mou,Yaoting Gui,Ruiying Diao,Honggang Li,Lihua Yang,Nie Xie,Zhiming Cai,Yuchen Liu,Eugene Yujun Xu

doi:10.1371/journal.pone.0133997

Abstract

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.

Highlights

The incidence of infertility is approximately 15% to 20% for couples of childbearing age, and about half of cases of infertility are caused by male factors [1, 2]
To examine whether DAX-1 genetic defects are associated with secretory azoospermia, we screened for DAX-1 exonic mutations in 776 secretory azoospermia patients and 709 men with proven fertility using massively parallel sequencing technology
Bioinformatic assessment of the variants indicated that the mutations C104W, E256Q and V385L were possibly damaging to the protein predicted by both Polyphen 2.0[24] and MutationTaster[25] (Table 2)

Summary

Introduction

The incidence of infertility is approximately 15% to 20% for couples of childbearing age, and about half of cases of infertility are caused by male factors [1, 2]. Secretory azoospermia, characterized by the absence of spermatozoa in semen, is a severe form of male infertility that affects approximately 1% of adult men in the general population [1, 2]. Previous studies have shown that genetic factors play an important role in IA [3]. Mutations in DAX-1 cause X-linked adrenal hypoplasia congenita (AHC), a disorder characterized by primary adrenal failure, hypogonadotropic hypogonadism and azoospermia [7]. Accumulating evidence from studies of Dax-1 knockout mice and those

Methods

Results

Conclusion