[一个中国智力障碍家系的两个新变异的遗传分析]。

Xiaoxiao Lyu, Chenyang Xu, Yunzhi Xu, Yanbao Xiang
{"title":"[一个中国智力障碍家系的两个新变异的遗传分析]。","authors":"Xiaoxiao Lyu, Chenyang Xu, Yunzhi Xu, Yanbao Xiang","doi":"10.3760/cma.j.cn511374-20240709-00381","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical phenotype and genetic characteristics of two siblings with intellectual disability.</p><p><strong>Methods: </strong>Clinical data and peripheral blood samples were collected from the proband, his younger sister and parents whom had presented at Wenzhou Central Hospital in February 2024. Low-coverage massively parallel copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) were carried out for the family. Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was performed on a fetus upon the couple's subsequent pregnancy. The study was approved by the Medical Ethics Committee of Wenzhou Central Hospital (Ethic No. L2024-07-001).</p><p><strong>Results: </strong>The proband was a 12-year-old boy who had presented with mental retardation and language delay. His 10-year-old sister also manifested delayed mental and motor development. Whole exome sequencing revealed that the proband and his sister had respectively harbored a novel heterozygous c.3549_3550del (p.Glu1183Aspfs*29) variant of the TRIP12 gene and a novel heterozygous c.99del (p.Ser34Alafs*38) variant of the GRIN2B gene. Sanger sequencing confirmed that both variants had a de novo origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+PS2_Supporting+PM2_Supporting). Neither variant was found to be carried by the fetus upon prenatal diagnosis.</p><p><strong>Conclusion: </strong>Above variants probably underlay the mental disorders in the two siblings, and the concurrent occurrence of two novel pathogenic variants in a family has been extremely rare.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 12","pages":"1456-1462"},"PeriodicalIF":0.0000,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"[Genetic analysis of two novel variants in a Chinese pedigree affected with intellectual disorder].\",\"authors\":\"Xiaoxiao Lyu, Chenyang Xu, Yunzhi Xu, Yanbao Xiang\",\"doi\":\"10.3760/cma.j.cn511374-20240709-00381\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To explore the clinical phenotype and genetic characteristics of two siblings with intellectual disability.</p><p><strong>Methods: </strong>Clinical data and peripheral blood samples were collected from the proband, his younger sister and parents whom had presented at Wenzhou Central Hospital in February 2024. Low-coverage massively parallel copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) were carried out for the family. Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was performed on a fetus upon the couple's subsequent pregnancy. The study was approved by the Medical Ethics Committee of Wenzhou Central Hospital (Ethic No. L2024-07-001).</p><p><strong>Results: </strong>The proband was a 12-year-old boy who had presented with mental retardation and language delay. His 10-year-old sister also manifested delayed mental and motor development. Whole exome sequencing revealed that the proband and his sister had respectively harbored a novel heterozygous c.3549_3550del (p.Glu1183Aspfs*29) variant of the TRIP12 gene and a novel heterozygous c.99del (p.Ser34Alafs*38) variant of the GRIN2B gene. Sanger sequencing confirmed that both variants had a de novo origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+PS2_Supporting+PM2_Supporting). Neither variant was found to be carried by the fetus upon prenatal diagnosis.</p><p><strong>Conclusion: </strong>Above variants probably underlay the mental disorders in the two siblings, and the concurrent occurrence of two novel pathogenic variants in a family has been extremely rare.</p>\",\"PeriodicalId\":39319,\"journal\":{\"name\":\"中华医学遗传学杂志\",\"volume\":\"41 12\",\"pages\":\"1456-1462\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-12-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"中华医学遗传学杂志\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3760/cma.j.cn511374-20240709-00381\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"中华医学遗传学杂志","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3760/cma.j.cn511374-20240709-00381","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0

摘要

目的:探讨两名智力残疾兄弟姐妹的临床表型和遗传特征。方法:收集2024年2月在温州市中心医院就诊的先证者、其妹妹及父母的临床资料和外周血。对该家族进行了低覆盖率大规模平行拷贝数变异测序(CNV-seq)和全外显子组测序(WES)。候选变异通过Sanger测序进行验证。在这对夫妇随后的怀孕中对胎儿进行了产前诊断。本研究经温州市中心医院医学伦理委员会批准(伦理号:No. 5)。l2024 - 07 - 001)。结果:先证者为一名12岁的男孩,表现为智力迟钝和语言迟缓。他10岁的妹妹也表现出智力和运动发育迟缓。全外显子组测序结果显示,先显子及其姊妹分别携带一种新的杂合型c.3549_3550del (p.Glu1183Aspfs*29)的TRIP12基因变异和一种新的杂合型c.99del (p.Ser34Alafs*38)的GRIN2B基因变异。桑格测序证实,这两种变异都是从头开始的。根据美国医学遗传学与基因组学学会(ACMG)的指南,这两种变异被归类为致病性(PVS1+ ps2_support + pm2_support)。在产前诊断时,没有发现两种变异是由胎儿携带的。结论:上述变异可能是两兄弟姐妹精神障碍的基础,在一个家族中同时出现两种新的致病变异是极为罕见的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
[Genetic analysis of two novel variants in a Chinese pedigree affected with intellectual disorder].

Objective: To explore the clinical phenotype and genetic characteristics of two siblings with intellectual disability.

Methods: Clinical data and peripheral blood samples were collected from the proband, his younger sister and parents whom had presented at Wenzhou Central Hospital in February 2024. Low-coverage massively parallel copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) were carried out for the family. Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was performed on a fetus upon the couple's subsequent pregnancy. The study was approved by the Medical Ethics Committee of Wenzhou Central Hospital (Ethic No. L2024-07-001).

Results: The proband was a 12-year-old boy who had presented with mental retardation and language delay. His 10-year-old sister also manifested delayed mental and motor development. Whole exome sequencing revealed that the proband and his sister had respectively harbored a novel heterozygous c.3549_3550del (p.Glu1183Aspfs*29) variant of the TRIP12 gene and a novel heterozygous c.99del (p.Ser34Alafs*38) variant of the GRIN2B gene. Sanger sequencing confirmed that both variants had a de novo origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+PS2_Supporting+PM2_Supporting). Neither variant was found to be carried by the fetus upon prenatal diagnosis.

Conclusion: Above variants probably underlay the mental disorders in the two siblings, and the concurrent occurrence of two novel pathogenic variants in a family has been extremely rare.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
相关文献
二甲双胍通过HDAC6和FoxO3a转录调控肌肉生长抑制素诱导肌肉萎缩
IF 8.9 1区 医学Journal of Cachexia, Sarcopenia and MusclePub Date : 2021-11-02 DOI: 10.1002/jcsm.12833
Min Ju Kang, Ji Wook Moon, Jung Ok Lee, Ji Hae Kim, Eun Jeong Jung, Su Jin Kim, Joo Yeon Oh, Sang Woo Wu, Pu Reum Lee, Sun Hwa Park, Hyeon Soo Kim
具有疾病敏感单倍型的非亲属供体脐带血移植后的1型糖尿病
IF 3.2 3区 医学Journal of Diabetes InvestigationPub Date : 2022-11-02 DOI: 10.1111/jdi.13939
Kensuke Matsumoto, Taisuke Matsuyama, Ritsu Sumiyoshi, Matsuo Takuji, Tadashi Yamamoto, Ryosuke Shirasaki, Haruko Tashiro
封面:蛋白质组学分析确定IRSp53和fastin是PRV输出和直接细胞-细胞传播的关键
IF 3.4 4区 生物学ProteomicsPub Date : 2019-12-02 DOI: 10.1002/pmic.201970201
Fei-Long Yu, Huan Miao, Jinjin Xia, Fan Jia, Huadong Wang, Fuqiang Xu, Lin Guo
来源期刊
中华医学遗传学杂志
中华医学遗传学杂志 Medicine-Medicine (all)
CiteScore
0.50
自引率
0.00%
发文量
9521
期刊介绍: Chinese Journal of Medical Genetics is a medical journal, founded in 1984, under the supervision of the China Association for Science and Technology, sponsored by the Chinese Medical Association (hosted by Sichuan University), and is now a monthly magazine, which attaches importance to academic orientation, adheres to the scientific, scholarly, advanced, and innovative, and has a certain degree of influence in the industry. Chinese Journal of Medical Genetics is a journal of Peking University, and is now included in Peking University Journal (Chinese Journal of Humanities and Social Sciences), CSCD Source Journals of Chinese Science Citation Database (with extended version), Statistical Source Journals (China Science and Technology Dissertation Outstanding Journals), Zhi.com (in Chinese), Wipu (in Chinese), Wanfang (in Chinese), CA Chemical Abstracts (U.S.), JST (Japan Science and Technology Science and Technology), and JST (Japan Science and Technology Science and Technology Research Center). ), JST (Japan Science and Technology Agency), Pж (AJ) Abstracts Journal (Russia), Copernicus Index (Poland), Cambridge Scientific Abstracts, Abstracts and Citation Database, Abstracts Magazine, Medical Abstracts, and so on.
期刊最新文献
[Clinical and genetic characteristics analysis of two children with comorbidity of two rare genetic diseases]. [Genetic analysis of a child with Leukoencephalopathy with ataxia caused by a homozygous variant of CLCN2 gene and a literature review]. [Clinical and genetic analysis of a child with Lamb-Shaffer syndrome due to a de novo variant of SOX5 gene]. [Clinical significance of trisomy 7 signaled by non-invasive prenatal testing and a literature review]. [Expert consensus on the standardized application of whole exome sequencing technology in diagnosis of genetic disorders].
×
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
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1