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Loss-of-function variants in KCTD19 cause non-obstructive azoospermia in humans
Azoospermia is a significant cause of male infertility, with non-obstructive azoospermia (NOA) being the most severe type of spermatogenic failure. NOA is mostly caused by congenital factors, but our understanding of its genetic causes is very limited. Here, we identified a frameshift variant (c.201...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10362269/ https://www.ncbi.nlm.nih.gov/pubmed/37485353 http://dx.doi.org/10.1016/j.isci.2023.107193 |
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author | Liu, Junyan Rahim, Fazal Zhou, Jianteng Fan, Suixing Jiang, Hanwei Yu, Changping Chen, Jing Xu, Jianze Yang, Gang Shah, Wasim Zubair, Muhammad Khan, Asad Li, Yang Shah, Basit Zhao, Daren Iqbal, Furhan Jiang, Xiaohua Guo, Tonghang Xu, Peng Xu, Bo Wu, Limin Ma, Hui Zhang, Yuanwei Zhang, Huan Shi, Qinghua |
author_facet | Liu, Junyan Rahim, Fazal Zhou, Jianteng Fan, Suixing Jiang, Hanwei Yu, Changping Chen, Jing Xu, Jianze Yang, Gang Shah, Wasim Zubair, Muhammad Khan, Asad Li, Yang Shah, Basit Zhao, Daren Iqbal, Furhan Jiang, Xiaohua Guo, Tonghang Xu, Peng Xu, Bo Wu, Limin Ma, Hui Zhang, Yuanwei Zhang, Huan Shi, Qinghua |
author_sort | Liu, Junyan |
collection | PubMed |
description | Azoospermia is a significant cause of male infertility, with non-obstructive azoospermia (NOA) being the most severe type of spermatogenic failure. NOA is mostly caused by congenital factors, but our understanding of its genetic causes is very limited. Here, we identified a frameshift variant (c.201_202insAC, p.Tyr68Thrfs∗17) and two nonsense variants (c.1897C>T, p.Gln633∗; c.2005C>T, p.Gln669∗) in KCTD19 (potassium channel tetramerization domain containing 19) from two unrelated infertile Chinese men and a consanguineous Pakistani family with three infertile brothers. Testicular histological analyses revealed meiotic metaphase I (MMI) arrest in the affected individuals. Mice modeling KCTD19 variants recapitulated the same MMI arrest phenotype due to severe disrupted individualization of MMI chromosomes. Further analysis showed a complete loss of KCTD19 protein in both Kctd19 mutant mouse testes and affected individual testes. Collectively, our findings demonstrate the pathogenicity of the identified KCTD19 variants and highlight an essential role of KCTD19 in MMI chromosome individualization. |
format | Online Article Text |
id | pubmed-10362269 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-103622692023-07-23 Loss-of-function variants in KCTD19 cause non-obstructive azoospermia in humans Liu, Junyan Rahim, Fazal Zhou, Jianteng Fan, Suixing Jiang, Hanwei Yu, Changping Chen, Jing Xu, Jianze Yang, Gang Shah, Wasim Zubair, Muhammad Khan, Asad Li, Yang Shah, Basit Zhao, Daren Iqbal, Furhan Jiang, Xiaohua Guo, Tonghang Xu, Peng Xu, Bo Wu, Limin Ma, Hui Zhang, Yuanwei Zhang, Huan Shi, Qinghua iScience Article Azoospermia is a significant cause of male infertility, with non-obstructive azoospermia (NOA) being the most severe type of spermatogenic failure. NOA is mostly caused by congenital factors, but our understanding of its genetic causes is very limited. Here, we identified a frameshift variant (c.201_202insAC, p.Tyr68Thrfs∗17) and two nonsense variants (c.1897C>T, p.Gln633∗; c.2005C>T, p.Gln669∗) in KCTD19 (potassium channel tetramerization domain containing 19) from two unrelated infertile Chinese men and a consanguineous Pakistani family with three infertile brothers. Testicular histological analyses revealed meiotic metaphase I (MMI) arrest in the affected individuals. Mice modeling KCTD19 variants recapitulated the same MMI arrest phenotype due to severe disrupted individualization of MMI chromosomes. Further analysis showed a complete loss of KCTD19 protein in both Kctd19 mutant mouse testes and affected individual testes. Collectively, our findings demonstrate the pathogenicity of the identified KCTD19 variants and highlight an essential role of KCTD19 in MMI chromosome individualization. Elsevier 2023-06-28 /pmc/articles/PMC10362269/ /pubmed/37485353 http://dx.doi.org/10.1016/j.isci.2023.107193 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Liu, Junyan Rahim, Fazal Zhou, Jianteng Fan, Suixing Jiang, Hanwei Yu, Changping Chen, Jing Xu, Jianze Yang, Gang Shah, Wasim Zubair, Muhammad Khan, Asad Li, Yang Shah, Basit Zhao, Daren Iqbal, Furhan Jiang, Xiaohua Guo, Tonghang Xu, Peng Xu, Bo Wu, Limin Ma, Hui Zhang, Yuanwei Zhang, Huan Shi, Qinghua Loss-of-function variants in KCTD19 cause non-obstructive azoospermia in humans |
title | Loss-of-function variants in KCTD19 cause non-obstructive azoospermia in humans |
title_full | Loss-of-function variants in KCTD19 cause non-obstructive azoospermia in humans |
title_fullStr | Loss-of-function variants in KCTD19 cause non-obstructive azoospermia in humans |
title_full_unstemmed | Loss-of-function variants in KCTD19 cause non-obstructive azoospermia in humans |
title_short | Loss-of-function variants in KCTD19 cause non-obstructive azoospermia in humans |
title_sort | loss-of-function variants in kctd19 cause non-obstructive azoospermia in humans |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10362269/ https://www.ncbi.nlm.nih.gov/pubmed/37485353 http://dx.doi.org/10.1016/j.isci.2023.107193 |
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