A novel homozygous TSGA10 missense variant causes acephalic spermatozoa syndrome in a Pakistani family.

IF 2.4 3区 医学 Q2 ANDROLOGY
Khalid Khan, Xiangjun Zhang, Sobia Dil, Ihsan Khan, Ahsanullah Unar, Jingwei Ye, Aurang Zeb, Muhammad Zubair, Wasim Shah, Huan Zhang, Muzammil Ahmad Khan, Limin Wu, Bo Xu, Hui Ma, Zina Wen, Qinghua Shi
{"title":"A novel homozygous TSGA10 missense variant causes acephalic spermatozoa syndrome in a Pakistani family.","authors":"Khalid Khan, Xiangjun Zhang, Sobia Dil, Ihsan Khan, Ahsanullah Unar, Jingwei Ye, Aurang Zeb, Muhammad Zubair, Wasim Shah, Huan Zhang, Muzammil Ahmad Khan, Limin Wu, Bo Xu, Hui Ma, Zina Wen, Qinghua Shi","doi":"10.1186/s12610-024-00220-7","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Acephalic spermatozoa syndrome is a rare type of teratozoospermia causing male infertility due to detachment of the sperm head and flagellum, which precludes fertilization potential. Although loss-of-function variations in several genes, including TSGA10, have been associated with acephalic spermatozoa syndrome, the genetic cause of many cases remains unclear.</p><p><strong>Results: </strong>We recruited a Pakistani family with two infertile brothers who suffered from acephalic spermatozoa syndrome. Through whole-exome sequencing (WES) followed by Sanger sequencing, we identified a novel missense variant in TSGA10 (c.1112T > C, p. Leu371Pro), which recessively co-segregated with the acephalic spermatozoa syndrome within this family. Ultrastructural analyses of spermatozoa from the patient revealed that 98% of flagellar cross-sections displayed abnormal axonemal ultrastructure, in addition to the head-flagellum detachment. Real-time quantitative PCR analysis revealed almost no detectable TSAG10 mRNA and western blot analysis also failed to detect TSAG10 protein in patient's sperm samples while TSGA10 expression was clearly detected in control samples. Consistently, immunofluorescence analysis demonstrated the presence of TSGA10 signal in the midpiece of sperm from the control but a complete absence of TSGA10 signal in sperm from the patient.</p><p><strong>Conclusion: </strong>Altogether, our study identifies a novel TSGA10 pathogenic variant as a cause of acephalic spermatozoa syndrome in this family and provides information regarding the clinical manifestations associated with TSGA10 variants in human.</p>","PeriodicalId":8730,"journal":{"name":"Basic and Clinical Andrology","volume":null,"pages":null},"PeriodicalIF":2.4000,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10840149/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Basic and Clinical Andrology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12610-024-00220-7","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ANDROLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Acephalic spermatozoa syndrome is a rare type of teratozoospermia causing male infertility due to detachment of the sperm head and flagellum, which precludes fertilization potential. Although loss-of-function variations in several genes, including TSGA10, have been associated with acephalic spermatozoa syndrome, the genetic cause of many cases remains unclear.

Results: We recruited a Pakistani family with two infertile brothers who suffered from acephalic spermatozoa syndrome. Through whole-exome sequencing (WES) followed by Sanger sequencing, we identified a novel missense variant in TSGA10 (c.1112T > C, p. Leu371Pro), which recessively co-segregated with the acephalic spermatozoa syndrome within this family. Ultrastructural analyses of spermatozoa from the patient revealed that 98% of flagellar cross-sections displayed abnormal axonemal ultrastructure, in addition to the head-flagellum detachment. Real-time quantitative PCR analysis revealed almost no detectable TSAG10 mRNA and western blot analysis also failed to detect TSAG10 protein in patient's sperm samples while TSGA10 expression was clearly detected in control samples. Consistently, immunofluorescence analysis demonstrated the presence of TSGA10 signal in the midpiece of sperm from the control but a complete absence of TSGA10 signal in sperm from the patient.

Conclusion: Altogether, our study identifies a novel TSGA10 pathogenic variant as a cause of acephalic spermatozoa syndrome in this family and provides information regarding the clinical manifestations associated with TSGA10 variants in human.

一种新型同卵 TSGA10 错义变异导致一个巴基斯坦家族出现畸形精子症。
背景:畸形精子症是一种罕见的畸形精子症,由于精子头部和鞭毛分离而导致男性不育,从而影响受精能力。尽管包括 TSGA10 在内的多个基因的功能缺失变异与畸形精子症有关,但许多病例的遗传原因仍不清楚:结果:我们招募了一个巴基斯坦家庭,其中有两兄弟患有畸形精子症,但都不能生育。通过全外显子组测序(WES)和桑格测序,我们发现了 TSGA10 中的一个新型错义变异(c.1112T > C, p. Leu371Pro),该变异与该家族中的 "畸形精子症 "呈隐性共分离。对患者精子的超微结构分析表明,除了头-鞭毛分离外,98%的鞭毛横切面显示出异常的轴丝超微结构。实时定量PCR分析显示,患者精子样本中几乎检测不到TSAG10 mRNA,Western印迹分析也未能检测到TSAG10蛋白,而对照样本中却能清楚地检测到TSGA10的表达。同样,免疫荧光分析表明,对照组精子中段存在 TSGA10 信号,但患者精子中完全没有 TSGA10 信号:总之,我们的研究确定了一种新型 TSGA10 致病变体是导致该家族出现畸形精子症的原因,并提供了与人类 TSGA10 变体相关的临床表现信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Basic and Clinical Andrology
Basic and Clinical Andrology Medicine-Urology
CiteScore
3.50
自引率
0.00%
发文量
21
审稿时长
22 weeks
期刊介绍: Basic and Clinical Andrology is an open access journal in the domain of andrology covering all aspects of male reproductive and sexual health in both human and animal models. The journal aims to bring to light the various clinical advancements and research developments in andrology from the international community.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信