Identification of KISS1R gene mutations in disorders of non-obstructive azoospermia in the northeast population of China.

Publisher: Wiley Country of Publication: United States NLM ID: 8801384 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-2825 (Electronic) Linking ISSN: 08878013 NLM ISO Abbreviation: J Clin Lab Anal Subsets: MEDLINE

Publication: Hoboken, N.J. : Wiley
Original Publication: New York : Alan R. Liss, Inc., c1987-

Genetic Predisposition to Disease*; Azoospermia/*genetics ; Mutation/*genetics ; Receptors, Kisspeptin-1/*genetics; Adult ; Azoospermia/blood ; Base Sequence ; China ; Hormones/blood ; Humans ; Software ; Spermatogenesis/genetics

Background: Non-obstructive azoospermia (NOA), a serious phenotype of male spermatogenesis failure, is a multifactorial disease which is regulated by genetic, epigenetic, and environmental factors. Some gene structural variants have been demonstrated to be related to NOA. Loss-of-function mutations of KISS1R cause normosmic idiopathic hypogonadotropic hypogonadism (IHH) which result in azoospermia at the pre-testicular level. The objective of this research was to investigate genetic variants of KISS1R in NOA patients.
Methods: The entire coding region of 52 spermatogenesis-associated genes (KISS1R included) was sequenced from 200 NOA patients. Mutation screening was performed to identify genetic variations of these genes by targeted exome sequencing. Sequencing data analysis was carried out by a series of bioinformatics tools. Candidate variants confirmation was performed by Sanger sequencing. Functional analysis of candidate variants was evaluated using SIFT and PolyPhen-2.
Results: Three heterozygous missense variants in KISS1R were identified in three patients, respectively. No deleterious variations in other candidate genes were found in the three patients. Two of these three variants, p.A211T and p.G186E, had been reported in the ExAC and dbSNP database, respectively, while the other variant p.A301D was novel. These variants were all predicted to be likely pathogenic by in silico analysis.
Conclusion: Our study revealed three heterozygous missense variants in KISS1R which expanded the mutation spectrum of KISS1R in infertile men with NOA in the northeast of China.
(© 2019 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.)

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2016YFC1000601 the National Key Research and Development Program of China

Keywords: KISS1R; NOA; male infertility; mutation; targeted exome sequencing

0 (Hormones)
0 (KISS1R protein, human)
0 (Receptors, Kisspeptin-1)

Azoospermia, Nonobstructive

Date Created: 20191211 Date Completed: 20210127 Latest Revision: 20210127

20250114

PMC7171332

10.1002/jcla.23139

31821609