Sequence variants of ZMYND15 cause azoospermia in humans, but they have not yet been reported in infertile men with severe oligozoospermia (SO).We performed whole-exome and Sanger sequencing to identify suspected causative variants in 414 idiopathic participating infertile men with SO or azoospermia. Three novel homozygous truncating variants in ZMYND15 were identified in three of the 219 (1.37%) unrelated patients with SO,including c.1209T>A(p.Tyr403*), c.1650delC (p.Glu551Lysfs*75), and c.1622_1636delinsCCAC (p.Leu541Profs*39). In silico bioinformatic analyses as well as in vivo and in vitro experiments showed that the ZMYND15 variants carried by the affected subjects might be the underling cause for their infertility.One patient accepted intracytoplasmic sperm injection(ICSI) therapy using his ejaculated sperm and his wife successfully became pregnant. Our findings expand the disease phenotype spectrum by indicating that ZMYND15 variants cause SO and male infertility and suggest a possible correlation between the severity of male infertility caused by ZMYND15 variants and male age. This article is protected by copyright. All rights reserved.
Human mutation. 2020 Nov 10 [Epub ahead of print]
Tong-Yao Hu, Huan Zhang, Lan-Lan Meng, Shi-Min Yuan, Chao-Feng Tu, Juan Du, Guang-Xiu Lu, Ge Lin, Hong-Chuan Nie, Yue-Qiu Tan
Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, China., Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China.