需要心脏移植的终末期心肌病的基因贡献。

IF 6 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Circulation: Genomic and Precision Medicine Pub Date : 2023-10-01 Epub Date: 2023-09-28 DOI:10.1161/CIRCGEN.123.004062
Yuri Kim, Oddný Brattberg Gunnarsdóttir, Anissa Viveiros, Daniel Reichart, Daniel Quiat, Jon A L Willcox, Hao Zhang, Huachen Chen, Justin J Curran, Daniel H Kim, Simon Urschel, Barbara McDonough, Joshua Gorham, Steven R DePalma, Jonathan G Seidman, Christine E Seidman, Gavin Y Oudit
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引用次数: 0

摘要

背景:许多心血管疾病促使晚期心力衰竭的发展,需要心脏移植。当可治疗的病因被排除在外时,定义病因的研究往往被放弃,从而被诊断为终末期特发性心肌病。我们研究了DNA序列分析是否可以确定需要心脏移植的终末期非缺血性心肌病的未识别原因,以及遗传原因的患病率是否与动态心肌病病例不同。方法:我们对来自一个中心的101名成人和21名儿童特发性心肌病患者的122颗移植心脏进行了全外显子组和基因组测序。分析了细胞核和线粒体基因组中的致病性/可能致病性变体的数据,并评估了非人微生物序列。在不同临床严重程度的心肌病队列中比较破坏性基因变异的频率。结果:54个样本(44.3%)存在致病性/可能致病性心肌病基因变异。致病性变异在儿童(42.9%)和成人(43.6%)样本中的频率相似,但突变基因的分布不同(P=8.30×(结论:45.9%的不明原因终末期心肌病患者发现了致病性变异和病毒性心肌炎。与动态心肌病患者相比,移植患者中受损基因变异的频率明显更高。基因分析有助于确定终末期心肌病的病因,指导患者和家庭成员的管理和风险分层。)ers。
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Genetic Contribution to End-Stage Cardiomyopathy Requiring Heart Transplantation.

Background: Many cardiovascular disorders propel the development of advanced heart failure that necessitates cardiac transplantation. When treatable causes are excluded, studies to define causes are often abandoned, resulting in a diagnosis of end-stage idiopathic cardiomyopathy. We studied whether DNA sequence analyses could identify unrecognized causes of end-stage nonischemic cardiomyopathy requiring heart transplantation and whether the prevalence of genetic causes differed from ambulatory cardiomyopathy cases.

Methods: We performed whole exome and genome sequencing of 122 explanted hearts from 101 adult and 21 pediatric patients with idiopathic cardiomyopathy from a single center. Data were analyzed for pathogenic/likely pathogenic variants in nuclear and mitochondrial genomes and assessed for nonhuman microbial sequences. The frequency of damaging genetic variants was compared among cardiomyopathy cohorts with different clinical severity.

Results: Fifty-four samples (44.3%) had pathogenic/likely pathogenic cardiomyopathy gene variants. The frequency of pathogenic variants was similar in pediatric (42.9%) and adult (43.6%) samples, but the distribution of mutated genes differed (P=8.30×10-4). The prevalence of causal genetic variants was significantly higher in end-stage than in previously reported ambulatory adult dilated cardiomyopathy cases (P<0.001). Among remaining samples with unexplained causes, no damaging mitochondrial variants were identified, but 28 samples contained parvovirus genome sequences, including 2 samples with 6- to 9-fold higher levels than the overall mean levels in other samples.

Conclusions: Pathogenic variants and viral myocarditis were identified in 45.9% of patients with unexplained end-stage cardiomyopathy. Damaging gene variants are significantly more frequent among transplant compared with patients with ambulatory cardiomyopathy. Genetic analyses can help define cause of end-stage cardiomyopathy to guide management and risk stratification of patients and family members.

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来源期刊
Circulation: Genomic and Precision Medicine
Circulation: Genomic and Precision Medicine Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
9.20
自引率
5.40%
发文量
144
期刊介绍: Circulation: Genomic and Precision Medicine is a distinguished journal dedicated to advancing the frontiers of cardiovascular genomics and precision medicine. It publishes a diverse array of original research articles that delve into the genetic and molecular underpinnings of cardiovascular diseases. The journal's scope is broad, encompassing studies from human subjects to laboratory models, and from in vitro experiments to computational simulations. Circulation: Genomic and Precision Medicine is committed to publishing studies that have direct relevance to human cardiovascular biology and disease, with the ultimate goal of improving patient care and outcomes. The journal serves as a platform for researchers to share their groundbreaking work, fostering collaboration and innovation in the field of cardiovascular genomics and precision medicine.
期刊最新文献
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