Journal article

Publication year: 2023

Journal: Communications Biology

Volume number: 6

Issue number: 1

eISSN: 2399-3642

Open access status: Gold

DOI Link: https://doi.org/10.1038/s42003-023-04714-4

Publisher: Nature Research

Abstract: 

Analysing genetic data from 1,655 men with non-obstructive azoospermia (NOA) reveals four independent loss-of-function variants in DDX3Y, suggesting that it is a key gene in the AZFa region and should be considered in diagnostic workflows for NOA.

Non-obstructive azoospermia, the absence of sperm in the ejaculate due to disturbed spermatogenesis, represents the most severe form of male infertility. De novo microdeletions of the Y-chromosomal AZFa region are one of few well-established genetic causes for NOA and are routinely analysed in the diagnostic workup of affected men. So far, it is unclear which of the three genes located in the AZFa chromosomal region is indispensible for germ cell maturation. Here we present four different likely pathogenic loss-of-function variants in the AZFa gene DDX3Y identified by analysing exome sequencing data of more than 1,600 infertile men. Three of the patients underwent testicular sperm extraction and revealed the typical AZFa testicular Sertoli cell-only phenotype. One of the variants was proven to be de novo. Consequently, DDX3Y represents the AZFa key spermatogenic factor and screening for variants in DDX3Y should be included in the diagnostic workflow.

Harvard Citation style: Dicke, A., Pilatz, A., Wyrwoll, M., Punab, M., Ruckert, C., Nagirnaja, L., et al. (2023) DDX3Y is likely the key spermatogenic factor in the AZFa region that contributes to human non-obstructive azoospermia, Communications Biology, 6(1), Article 350. https://doi.org/10.1038/s42003-023-04714-4

APA Citation style: Dicke, A., Pilatz, A., Wyrwoll, M., Punab, M., Ruckert, C., Nagirnaja, L., Aston, K., Conrad, D., Di Persio, S., Neuhaus, N., Fietz, D., Laan, M., Stallmeyer, B., & Tuettelmann, F. (2023). DDX3Y is likely the key spermatogenic factor in the AZFa region that contributes to human non-obstructive azoospermia. Communications Biology. 6(1), Article 350. https://doi.org/10.1038/s42003-023-04714-4