A homozygous missense variant in DND1 causes non-obstructive azoospermia in humans

Xuefeng Xie; Mazhar Khan; Muhammad Zubair; Abbas Khan; Ranjha Khan; Jianteng Zhou; Yuanwei Zhang; Muzafar Said; Sher Ali Khan; Qamar Zaman; Ghulam Murtaza; Muzamil Ahmad Khan; Wei Liu; Xiaoning Hou; Huan Zhang; Bo Xu; Xiaohua Jiang; Shun Bai; Qinghua Shi

doi:10.3389/fgene.2022.1017302

A homozygous missense variant in DND1 causes non-obstructive azoospermia in humans

Front Genet. 2022 Sep 30:13:1017302. doi: 10.3389/fgene.2022.1017302. eCollection 2022.

Authors

Xuefeng Xie¹, Mazhar Khan¹, Muhammad Zubair¹, Abbas Khan², Ranjha Khan¹, Jianteng Zhou¹, Yuanwei Zhang¹, Muzafar Said³, Sher Ali Khan³, Qamar Zaman¹, Ghulam Murtaza¹, Muzamil Ahmad Khan⁴, Wei Liu¹, Xiaoning Hou¹, Huan Zhang¹, Bo Xu¹, Xiaohua Jiang¹, Shun Bai¹, Qinghua Shi¹

Affiliations

¹ The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China.
² Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
³ Malka Andrology, Fertility and IVF Center, Roshan Specialized Hospital, saidu sharif, Pakistan.
⁴ Gomal Centre of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan, Pakistan.

Abstract

Non-obstructive azoospermia (NOA) is a severe factor of male infertility; it affects approximately 1% of the global male population and accounts for 40% of male infertility cases. However, the majority of NOA cases remain idiopathic. This is the first study using whole-exome sequencing (WES) to identify a novel missense mutation in the DND1 gene (c.212A>C, p. E71A) from a Pakistani family, that includes three males with NOA. This mutation is predicted to cause DND1 protein misfolding and weaken the DND1 interaction with NANOS2, a significant regulator in primordial germ cell development. Our study identified a DND1 pathogenic mutation in NOA patients and highlighted its critical role in male fertility in humans.

Keywords: DND1; NOA; gene mutation; homozygous missense mutation; male infertility.