基因重新评估——难以捉摸的家族性扩张性心肌病导致纯合子AARS2变异的发现——定期重新评估遗传发现的重要性

IF 0.5 Q4 CARDIAC & CARDIOVASCULAR SYSTEMS Cardiogenetics Pub Date : 2021-07-23 DOI:10.3390/CARDIOGENETICS11030013
P. Bhardwaj, C. Vissing, N. K. Stampe, K. Rossing, A. Christensen, T. H. Jensen, B. Winkel
{"title":"基因重新评估——难以捉摸的家族性扩张性心肌病导致纯合子AARS2变异的发现——定期重新评估遗传发现的重要性","authors":"P. Bhardwaj, C. Vissing, N. K. Stampe, K. Rossing, A. Christensen, T. H. Jensen, B. Winkel","doi":"10.3390/CARDIOGENETICS11030013","DOIUrl":null,"url":null,"abstract":"Background: AARS2 encodes the mitochondrial protein alanyl-tRNA synthetase 2 (MT-AlaRS), an important enzyme in oxidative phosphorylation. Variants in AARS2 have previously been associated with infantile cardiomyopathy. Case summary: A 4-year-old girl died of infantile-onset dilated cardiomyopathy (DCM) in 1996. Fifteen years later, her 21-year-old brother was diagnosed with DCM and ultimately underwent heart transplantation. Initial sequencing of 15 genes discovered no pathogenic variants in the brother at the time of his diagnosis. However, 9 years later re-screening in an updated screening panel of 129 genes identified a homozygous AARS2 (c.1774C > T) variant. Sanger sequencing of the deceased girl confirmed her to be homozygous for the AARS2 variant, while both parents and a third sibling were all found to be unaffected heterozygous carriers of the AARS2 variant. Discussion: This report underlines the importance of repeated and extended genetic screening of elusive families with suspected hereditary cardiomyopathies, as our knowledge of disease-causing mutations continuously grows. Although identification of the genetic etiology in the reported family would not have changed the clinical management, the genetic finding allows genetic counselling and holds substantial value in identifying at-risk relatives.","PeriodicalId":41330,"journal":{"name":"Cardiogenetics","volume":" ","pages":""},"PeriodicalIF":0.5000,"publicationDate":"2021-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/CARDIOGENETICS11030013","citationCount":"0","resultStr":"{\"title\":\"Reassessment of Gene-Elusive Familial Dilated Cardiomyopathy Leading to the Discovery of a Homozygous AARS2 Variant—The Importance of Regular Reassessment of Genetic Findings\",\"authors\":\"P. Bhardwaj, C. Vissing, N. K. Stampe, K. Rossing, A. Christensen, T. H. Jensen, B. Winkel\",\"doi\":\"10.3390/CARDIOGENETICS11030013\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background: AARS2 encodes the mitochondrial protein alanyl-tRNA synthetase 2 (MT-AlaRS), an important enzyme in oxidative phosphorylation. Variants in AARS2 have previously been associated with infantile cardiomyopathy. Case summary: A 4-year-old girl died of infantile-onset dilated cardiomyopathy (DCM) in 1996. Fifteen years later, her 21-year-old brother was diagnosed with DCM and ultimately underwent heart transplantation. Initial sequencing of 15 genes discovered no pathogenic variants in the brother at the time of his diagnosis. However, 9 years later re-screening in an updated screening panel of 129 genes identified a homozygous AARS2 (c.1774C > T) variant. Sanger sequencing of the deceased girl confirmed her to be homozygous for the AARS2 variant, while both parents and a third sibling were all found to be unaffected heterozygous carriers of the AARS2 variant. Discussion: This report underlines the importance of repeated and extended genetic screening of elusive families with suspected hereditary cardiomyopathies, as our knowledge of disease-causing mutations continuously grows. Although identification of the genetic etiology in the reported family would not have changed the clinical management, the genetic finding allows genetic counselling and holds substantial value in identifying at-risk relatives.\",\"PeriodicalId\":41330,\"journal\":{\"name\":\"Cardiogenetics\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.5000,\"publicationDate\":\"2021-07-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.3390/CARDIOGENETICS11030013\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cardiogenetics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3390/CARDIOGENETICS11030013\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cardiogenetics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/CARDIOGENETICS11030013","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0

摘要

背景:AARS2编码线粒体蛋白丙氨酰tRNA合成酶2(MT-AlaRS),这是一种重要的氧化磷酸化酶。AARS2的变异先前与婴儿心肌病有关。病例摘要:1996年,一名4岁女孩死于婴儿期扩张型心肌病。15年后,她21岁的弟弟被诊断为扩张型心肌病,最终接受了心脏移植。对15个基因的初步测序发现,在他确诊时,在他的兄弟身上没有发现致病性变异。然而,9年后,在一个由129个基因组成的最新筛选小组中重新筛选,发现了一个纯合AARS2(c.1774C>T)变体。对死亡女孩的Sanger测序证实她是AARS2变体的纯合子,而父母和第三个兄弟姐妹都被发现是未受影响的AARS2变异的杂合子携带者。讨论:随着我们对致病突变的了解不断增加,这份报告强调了对疑似遗传性心肌病的难以捉摸的家族进行重复和扩展基因筛查的重要性。尽管在报告的家族中确定遗传病因不会改变临床管理,但遗传发现允许遗传咨询,并在确定高危亲属方面具有重要价值。
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
Reassessment of Gene-Elusive Familial Dilated Cardiomyopathy Leading to the Discovery of a Homozygous AARS2 Variant—The Importance of Regular Reassessment of Genetic Findings
Background: AARS2 encodes the mitochondrial protein alanyl-tRNA synthetase 2 (MT-AlaRS), an important enzyme in oxidative phosphorylation. Variants in AARS2 have previously been associated with infantile cardiomyopathy. Case summary: A 4-year-old girl died of infantile-onset dilated cardiomyopathy (DCM) in 1996. Fifteen years later, her 21-year-old brother was diagnosed with DCM and ultimately underwent heart transplantation. Initial sequencing of 15 genes discovered no pathogenic variants in the brother at the time of his diagnosis. However, 9 years later re-screening in an updated screening panel of 129 genes identified a homozygous AARS2 (c.1774C > T) variant. Sanger sequencing of the deceased girl confirmed her to be homozygous for the AARS2 variant, while both parents and a third sibling were all found to be unaffected heterozygous carriers of the AARS2 variant. Discussion: This report underlines the importance of repeated and extended genetic screening of elusive families with suspected hereditary cardiomyopathies, as our knowledge of disease-causing mutations continuously grows. Although identification of the genetic etiology in the reported family would not have changed the clinical management, the genetic finding allows genetic counselling and holds substantial value in identifying at-risk relatives.
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
来源期刊
Cardiogenetics
Cardiogenetics CARDIAC & CARDIOVASCULAR SYSTEMS-
自引率
0.00%
发文量
26
审稿时长
11 weeks
期刊最新文献
Gene-Specific Discriminative Echocardiogram Findings in Hypertrophic Cardiomyopathy Determined Using Artificial Intelligence: A Pilot Study Inherited Arrhythmogenic Syndromes From Natural History to Contemporary Management of Aortic Diseases: A State-of-the-Art Review of Thoracic Aortic Aneurysm Sudden Cardiac Death in Biventricular Arrhythmogenic Cardiomyopathy: A New Undescribed Variant of the MYH6 Gene A Family with a Single LMNA Mutation Illustrates Diversity in Cardiac Phenotypes Associated with Laminopathic Progeroid Syndromes
×
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