Association of ESX1 gene variants with non-obstructive azoospermia in Chinese males

Abstract Genetic factors are one of the most important causes of non-obstructive azoospermia (NOA). ESX1 is an X-linked testis-biased expressed gene, and a potential biomarker for testicular sperm retrieval in NOA patients, yet few systematic studies have investigated its association with NOA. Here,...

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Autores principales:	Qian Ma, Ye Du, Xiaomin Luo, Jing Ye, Yaoting Gui
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/228992510a284c979c0faed8768c854f
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spelling	oai:doaj.org-article:228992510a284c979c0faed8768c854f2021-12-02T15:53:43ZAssociation of ESX1 gene variants with non-obstructive azoospermia in Chinese males10.1038/s41598-021-84182-02045-2322https://doaj.org/article/228992510a284c979c0faed8768c854f2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84182-0https://doaj.org/toc/2045-2322Abstract Genetic factors are one of the most important causes of non-obstructive azoospermia (NOA). ESX1 is an X-linked testis-biased expressed gene, and a potential biomarker for testicular sperm retrieval in NOA patients, yet few systematic studies have investigated its association with NOA. Here, we performed selected exonic sequencing in a large cohort of Chinese males, and four novel missense mutations (including one compound mutation), one novel synonymous mutation of ESX1 unique to NOA patients were identified. We analyzed the effects of ESX1 mutations on cyclin A degradation and cell cycle progression by immunoprecipitation assay and flow cytometry, and found that the compound mutant p.[P365R; L366V] ESX1 compromised the stabilizing effect of ESX1 on polyubiquitinated cyclin A, thereby causing the failure of M phase arrest in cells. Further studies showed that the deleterious effect of the compound mutations on ESX1 protein function was attributed to p.P365R but not p.L366V alteration. The novel ESX1 mutation p.P365R might confer high risk for NOA in Han Chinese population, probably via affecting cell cycle control.Qian MaYe DuXiaomin LuoJing YeYaoting GuiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Qian Ma Ye Du Xiaomin Luo Jing Ye Yaoting Gui Association of ESX1 gene variants with non-obstructive azoospermia in Chinese males
description	Abstract Genetic factors are one of the most important causes of non-obstructive azoospermia (NOA). ESX1 is an X-linked testis-biased expressed gene, and a potential biomarker for testicular sperm retrieval in NOA patients, yet few systematic studies have investigated its association with NOA. Here, we performed selected exonic sequencing in a large cohort of Chinese males, and four novel missense mutations (including one compound mutation), one novel synonymous mutation of ESX1 unique to NOA patients were identified. We analyzed the effects of ESX1 mutations on cyclin A degradation and cell cycle progression by immunoprecipitation assay and flow cytometry, and found that the compound mutant p.[P365R; L366V] ESX1 compromised the stabilizing effect of ESX1 on polyubiquitinated cyclin A, thereby causing the failure of M phase arrest in cells. Further studies showed that the deleterious effect of the compound mutations on ESX1 protein function was attributed to p.P365R but not p.L366V alteration. The novel ESX1 mutation p.P365R might confer high risk for NOA in Han Chinese population, probably via affecting cell cycle control.
format	article
author	Qian Ma Ye Du Xiaomin Luo Jing Ye Yaoting Gui
author_facet	Qian Ma Ye Du Xiaomin Luo Jing Ye Yaoting Gui
author_sort	Qian Ma
title	Association of ESX1 gene variants with non-obstructive azoospermia in Chinese males
title_short	Association of ESX1 gene variants with non-obstructive azoospermia in Chinese males
title_full	Association of ESX1 gene variants with non-obstructive azoospermia in Chinese males
title_fullStr	Association of ESX1 gene variants with non-obstructive azoospermia in Chinese males
title_full_unstemmed	Association of ESX1 gene variants with non-obstructive azoospermia in Chinese males
title_sort	association of esx1 gene variants with non-obstructive azoospermia in chinese males
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/228992510a284c979c0faed8768c854f
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Association of ESX1 gene variants with non-obstructive azoospermia in Chinese males

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