[基因名称]中的功能丧失变异导致人类非梗阻性无精子症。 （注：原文中“in”后面缺少具体基因名称，这里用[基因名称]代替以便完整表达意思）
Loss-of-function variants in cause non-obstructive azoospermia in humans.
作者信息
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
机构信息
Division of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei 230027, China.
Institute of Pure and Applied Biology, Zoology Division, Bahauddin Zakariya University, Multan 60800, Pakistan.
出版信息
iScience. 2023 Jun 28;26(7):107193. doi: 10.1016/j.isci.2023.107193. eCollection 2023 Jul 21.
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 (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 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 mutant mouse testes and affected individual testes. Collectively, our findings demonstrate the pathogenicity of the identified variants and highlight an essential role of in MMI chromosome individualization.
无精子症是男性不育的一个重要原因，其中非梗阻性无精子症（NOA）是最严重的生精功能衰竭类型。NOA主要由先天性因素引起，但我们对其遗传原因的了解非常有限。在此，我们在两名不相关的中国不育男性以及一个有三名不育兄弟的巴基斯坦近亲家庭中，在（含钾通道四聚化结构域19）中鉴定出一个移码变异（c.201_202insAC，p.Tyr68Thrfs∗17）和两个无义变异（c.1897C>T，p.Gln633∗；c.2005C>T，p.Gln669∗）。睾丸组织学分析显示，受影响个体存在减数分裂中期I（MMI）阻滞。携带变异的小鼠模型由于MMI染色体的严重个体化破坏而重现了相同的MMI阻滞表型。进一步分析表明，在携带突变的小鼠睾丸和受影响个体的睾丸中，KCTD19蛋白完全缺失。总体而言，我们的研究结果证明了所鉴定变异的致病性，并突出了KCTD19在MMI染色体个体化中的重要作用。
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