A novel homozygous mutation in the meiotic gene MSH4 leading to male infertility due to non-obstructive azoospermia.

A novel homozygous mutation in the meiotic gene MSH4 leading to male infertility due to non-obstructive azoospermia. Am J Transl Res. 2020;12(12):8185-8191 Authors: Tang D, Xu C, Geng H, Gao Y, Cheng H, Ni X, He X, Cao Y Abstract Non-obstructive azoospermia (NOA) is the most severe form of male infertility. Although some causes have been established, including genetic causes, the etiology in most cases remains idiopathic. Mutations in MSH4 (OMIM: 602105), an important gene involved in meiosis, may be related to female infertility due to primary ovarian insufficiency (POI) and male NOA. Here, we report a novel homozygous stop-gain mutation of MSH4 associated with NOA. Whole exome sequencing (WES) and bioinformatic analysis were performed in a patient with NOA from a consanguineous family (F1 II-1). A rare homozygous MSH4 stop-gain mutation (c.1552C>T:p.Q518X) was observed in the patient, and his parents were heterozygous carriers, as verified by Sanger sequencing. Testicular biopsy and hematoxylin and eosin staining of testicular tissue suggested meiotic arrest (MA), and no sperm were observed. MSH4 was detected in other 50 separate cases with same pathological results of MA using the same procedures, but only one heterozygous mutation was observed. Subsequent real-time quantitative polymerase chain reaction and immunohistochemistry were performed to examine mRNA expression levels and the localization of the MSH4 protein in the tes...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research