心脏通道病的拷贝数变异:常规心律失常诊断中仍有遗漏。

IF 4.8 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Biomolecules Pub Date : 2024-11-15 DOI:10.3390/biom14111450
Maria Gnazzo, Giovanni Parlapiano, Francesca Di Lorenzo, Daniele Perrino, Silvia Genovese, Valentina Lanari, Daniela Righi, Federica Calì, Massimo Stefano Silvetti, Elena Falcone, Alessia Bauleo, Fabrizio Drago, Antonio Novelli, Anwar Baban
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引用次数: 0

摘要

遗传性心脏通道病是年轻人心脏性猝死(SCD)的主要原因。基因检测的重点是通过下一代测序(NGS)鉴定单核苷酸变异(SNV)。然而,遗传学上难以捉摸的病例可能携带拷贝数变异(CNV),这就需要特定的检测工具。我们通过调查文献数据和内部分析 KCNQ1、KCNH2、SCN5A 和 RYR2 中存在 CNVs 的队列,证明了识别 CNVs 的实用性。文献中报告了 119 例患者的 CNV,我们的队列中报告了 21 例患者的 CNV。KCNQ1中存在CNV的年轻患者表现为长QT(LQT)表型> 480毫秒,晕厥发生率较高。他们中没有人患有 SCD。所有 KCNH2 CNV 患者的 QT 表型均大于 480 毫秒。SCN5A 中的 CNV 表现为 Brugada 模式,主要发生在男性身上。相反,成年女性则表现出更多的室上性心律失常。RYR2-外显子3缺失表现出更广泛的表型,包括左心室不充盈(LVNC)和儿茶酚胺能多形性室性心动过速(CPVT)。小儿患者表现为房性心律失常和阵发性心房颤动。在年轻女性中,晕厥和SCA的发病率相对较高。CNVs 的检测在两类人群中更有价值:家族性通道病和疑似 Jervell 和 Lange-Nielsen 综合征或 CPVT 患者。由于报告的个体数量有限,今后必须进行多中心研究才能得出结论性结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Copy Number Variants in Cardiac Channelopathies: Still a Missed Part in Routine Arrhythmic Diagnostics.

Inherited cardiac channelopathies are major causes of sudden cardiac death (SCD) in young people. Genetic testing is focused on the identification of single-nucleotide variants (SNVs) by Next-Generation Sequencing (NGS). However, genetically elusive cases can carry copy number variants (CNVs), which need specific detection tools. We underlie the utility of identifying CNVs by investigating the literature data and internally analyzing cohorts with CNVs in KCNQ1, KCNH2, SCN5A, and RYR2. CNVs were reported in 119 patients from the literature and 21 from our cohort. Young patients with CNVs in KCNQ1 show a Long QT (LQT) phenotype > 480 ms and a higher frequency of syncope. None of them had SCD. All patients with CNV in KCNH2 had a positive phenotype for QT > 480 ms. CNVs in SCN5A were represented by the Brugada pattern, with major cardiac events mainly in males. Conversely, adult females show more supraventricular arrhythmias. RYR2-exon3 deletion showed a broader phenotype, including left ventricular non-compaction (LVNC) and catecholaminergic polymorphic ventricular tachycardia (CPVT). Pediatric patients showed atrial arrhythmias and paroxysmal atrial fibrillation. Relatively higher syncope and SCA were observed in young females. The detection of CNVs can be of greater yield in two groups: familial channelopathies and patients with suspected Jervell and Lange-Nielsen syndrome or CPVT. The limited number of reported individuals makes it mandatory for multicentric studies to give future conclusive results.

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来源期刊
Biomolecules
Biomolecules Biochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
9.40
自引率
3.60%
发文量
1640
审稿时长
18.28 days
期刊介绍: Biomolecules (ISSN 2218-273X) is an international, peer-reviewed open access journal focusing on biogenic substances and their biological functions, structures, interactions with other molecules, and their microenvironment as well as biological systems. Biomolecules publishes reviews, regular research papers and short communications.  Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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