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Novel Hemizygous Mutations of TEX11 Cause Meiotic Arrest and Non-obstructive Azoospermia in Chinese Han Population

Testis-expressed gene 11 (TEX11) mutation has been associated with non-obstructive azoospermia (NOA) and meiotic arrest. An analogous mutation of TEX11 in the mouse impairs meiosis and can be rescued by in vitro expansion of SSCs and gene therapy. However, a lack of genetic screening of a large coho...

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Autores principales: Ji, Zhiyong, Yao, Chencheng, Yang, Chao, Huang, Chuan, Zhao, Liangyu, Han, Xia, Zhu, Zijue, Zhi, Erlei, Liu, Nachuan, Zhou, Zhi, Li, Zheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491544/
https://www.ncbi.nlm.nih.gov/pubmed/34621296
http://dx.doi.org/10.3389/fgene.2021.741355
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author Ji, Zhiyong
Yao, Chencheng
Yang, Chao
Huang, Chuan
Zhao, Liangyu
Han, Xia
Zhu, Zijue
Zhi, Erlei
Liu, Nachuan
Zhou, Zhi
Li, Zheng
author_facet Ji, Zhiyong
Yao, Chencheng
Yang, Chao
Huang, Chuan
Zhao, Liangyu
Han, Xia
Zhu, Zijue
Zhi, Erlei
Liu, Nachuan
Zhou, Zhi
Li, Zheng
author_sort Ji, Zhiyong
collection PubMed
description Testis-expressed gene 11 (TEX11) mutation has been associated with non-obstructive azoospermia (NOA) and meiotic arrest. An analogous mutation of TEX11 in the mouse impairs meiosis and can be rescued by in vitro expansion of SSCs and gene therapy. However, a lack of genetic screening of a large cohort of Asian patients (including pedigree analysis) and proper functional evaluation limit the clinical application of TEX11 mutation screening. Thus, we performed whole-exome sequencing (WES) in 479 patients with NOA and identified three novel mutations (two splicing mutations and one missense mutation) in TEX11 in three pairs of siblings from three families and four novel pathogenic mutations (three frameshift mutations and a non-sense mutation) of TEX11 in four sporadic NOA-affected cases. Novel variants among family members were segregated by disease phenotype, and all the seven mutations were predicted to be pathogenic. Histological analysis showed that three patients with TEX11 mutations underwent meiotic arrest. The four mutations that resulted in protein truncations and defective meiosis-specific sporulation domain SPO22 were validated by Western blot. In total, we find seven of 479 patients of NOA (1.5%) carrying TEX11 mutations. Our study expands the knowledge of mutations of TEX11 gene in Asian patients with NOA. The high prevalence and X-linked inherited mode indicated that TEX11 might be included in genetic screening panels for the clinical evaluation of patients with NOA.
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spelling pubmed-84915442021-10-06 Novel Hemizygous Mutations of TEX11 Cause Meiotic Arrest and Non-obstructive Azoospermia in Chinese Han Population Ji, Zhiyong Yao, Chencheng Yang, Chao Huang, Chuan Zhao, Liangyu Han, Xia Zhu, Zijue Zhi, Erlei Liu, Nachuan Zhou, Zhi Li, Zheng Front Genet Genetics Testis-expressed gene 11 (TEX11) mutation has been associated with non-obstructive azoospermia (NOA) and meiotic arrest. An analogous mutation of TEX11 in the mouse impairs meiosis and can be rescued by in vitro expansion of SSCs and gene therapy. However, a lack of genetic screening of a large cohort of Asian patients (including pedigree analysis) and proper functional evaluation limit the clinical application of TEX11 mutation screening. Thus, we performed whole-exome sequencing (WES) in 479 patients with NOA and identified three novel mutations (two splicing mutations and one missense mutation) in TEX11 in three pairs of siblings from three families and four novel pathogenic mutations (three frameshift mutations and a non-sense mutation) of TEX11 in four sporadic NOA-affected cases. Novel variants among family members were segregated by disease phenotype, and all the seven mutations were predicted to be pathogenic. Histological analysis showed that three patients with TEX11 mutations underwent meiotic arrest. The four mutations that resulted in protein truncations and defective meiosis-specific sporulation domain SPO22 were validated by Western blot. In total, we find seven of 479 patients of NOA (1.5%) carrying TEX11 mutations. Our study expands the knowledge of mutations of TEX11 gene in Asian patients with NOA. The high prevalence and X-linked inherited mode indicated that TEX11 might be included in genetic screening panels for the clinical evaluation of patients with NOA. Frontiers Media S.A. 2021-09-21 /pmc/articles/PMC8491544/ /pubmed/34621296 http://dx.doi.org/10.3389/fgene.2021.741355 Text en Copyright © 2021 Ji, Yao, Yang, Huang, Zhao, Han, Zhu, Zhi, Liu, Zhou and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Ji, Zhiyong
Yao, Chencheng
Yang, Chao
Huang, Chuan
Zhao, Liangyu
Han, Xia
Zhu, Zijue
Zhi, Erlei
Liu, Nachuan
Zhou, Zhi
Li, Zheng
Novel Hemizygous Mutations of TEX11 Cause Meiotic Arrest and Non-obstructive Azoospermia in Chinese Han Population
title Novel Hemizygous Mutations of TEX11 Cause Meiotic Arrest and Non-obstructive Azoospermia in Chinese Han Population
title_full Novel Hemizygous Mutations of TEX11 Cause Meiotic Arrest and Non-obstructive Azoospermia in Chinese Han Population
title_fullStr Novel Hemizygous Mutations of TEX11 Cause Meiotic Arrest and Non-obstructive Azoospermia in Chinese Han Population
title_full_unstemmed Novel Hemizygous Mutations of TEX11 Cause Meiotic Arrest and Non-obstructive Azoospermia in Chinese Han Population
title_short Novel Hemizygous Mutations of TEX11 Cause Meiotic Arrest and Non-obstructive Azoospermia in Chinese Han Population
title_sort novel hemizygous mutations of tex11 cause meiotic arrest and non-obstructive azoospermia in chinese han population
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491544/
https://www.ncbi.nlm.nih.gov/pubmed/34621296
http://dx.doi.org/10.3389/fgene.2021.741355
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