基因检测对长QT综合征的临床影响——来自日本全国LQTS登记的证据。

IF 3.1 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Circulation Journal Pub Date : 2025-05-23 Epub Date: 2025-03-30 DOI:10.1253/circj.CJ-25-0105

Takeshi Aiba, Seiko Ohno, Misa Takegami, Yoshiaki Kato, Heima Sakaguchi, Keiko Shimamoto, Keiko Sonoda, Kazufumi Ida, Naokata Sumitomo, Taisuke Nabeshima, Takashi Murakami, Yumiko Ninomiya, Koichi Kato, Megumi Fukuyama, Takeru Makiyama, Kenshi Hayashi, Kunio Ohta, Hiroshi Morita, Tadashi Nakajima, Yoshiaki Kaneko, Nobue Yagihara, Sou Otsuki, Tomoki Kosho, Yoko Yoshida, Motoki Takamuro, Michihiko Ueno, Tatsunori Takahashi, Yasuya Inden, Yasunobu Hayabuchi, Shota Muraji, Shigeo Watanabe, Kunihiro Nishimura, Yoshihiro Asano, Hitoshi Horigome, Masao Yoshinaga, Minoru Horie, Wataru Shimizu, Kengo Kusano

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引用次数: 0

摘要

背景：基因检测对长QT综合征（LQTS）的诊断、风险分层和治疗策略是有用的。本研究探讨基因检测对LQTS患者的临床影响。方法与结果：共3851例患者(先证者：2316例[60%]；女性：2283人[59%]；诊断为LQTS （LQTS评分≥3.5,QTc≥500 ms， LQTS相关基因的致病变异，或QTc 480-499 ms的未发现晕厥）的患者入组本研究。在这些患者中，1146例（29.8%）发生晕厥，322例（8.5%）在≤70岁时发生心室颤动（VF）或心肺骤停（CPA）。使用下一代测序面板和/或Sanger测序对3,770例（98%）患者进行基因检测，然后确定以下lqts相关基因的基因型：KCNQ1 (45%), KCNH2 (34%), SCN5A (8%), KCNE1 (0.1%), KCNE2 (0.03%), KCNJ2 (2.7%), CACNA1C（1.2%）和CALM1,2（0.3%）。47例（1.2%）患者存在lqts相关基因的双杂合或复合杂合变异体，而220例（5.8%）患者的基因型未知。将表型与基因型进行比较，除CACNA1C外，CALM1 2患者的QTc明显长于其他患者，而KCNJ2患者的QTc几乎正常。首次心脏事件（晕厥、VF/CPA）的发生率在基因型中存在差异，且CALM1、2例患者的预后明显较差。结论：包括LQTS非主要基因在内的综合基因检测对LQTS的诊断和风险分层具有重要意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Clinical Impact of Genetic Testing for Long QT Syndrome　- Evidence From a Nationwide LQTS Registry in Japan.

Background: Genetic testing for long QT syndrome (LQTS) is useful for diagnosis, risk stratification, and therapeutic strategies. This study investigated the clinical impact of genetic testing for LQTS patients.

Methods and results: Total 3,851 patients (proband: 2,316 [60%]; female: 2,283 [59%]; median age: 14 years [interquartile range 9-36 years]) diagnosed with LQTS (LQTS score ≥3.5, QTc ≥500 ms, pathogenic variants in LQTS-associated genes, or unexplored syncope with QTc 480-499 ms) were enrolled in this study. Of these patients, 1,146 (29.8%) experienced syncope and 322 (8.5%) experienced ventricular fibrillation (VF) or cardiopulmonary arrest (CPA) at ≤70 years of age. Genetic testing using a next-generation sequencing panel and/or Sanger sequencing was performed for 3,770 (98%) patients, genotype was then identified in the following LQTS-associated genes: KCNQ1 (45%), KCNH2 (34%), SCN5A (8%), KCNE1 (0.1%), KCNE2 (0.03%), KCNJ2 (2.7%), CACNA1C (1.2%), and CALM1,2 (0.3%). Forty-seven (1.2%) patients had double or compound heterozygous variants in LQTS-associated genes, whereas the genotype remained unknown in 220 (5.8%) patients. When comparing phenotype with genotype, QTc was significantly longer in CALM1,2 patients than in others except for CACNA1C, whereas QTc was almost normal in KCNJ2 patients. The incidence of the first cardiac event (syncope, VF/CPA) differed among the genotypes, and prognosis was significantly worse for CALM1,2 patients.

Conclusions: Comprehensive genetic testing, including non-major LQTS genes, is important for diagnosis and risk stratification of LQTS.

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来源期刊

Circulation Journal 医学-心血管系统

CiteScore

5.80

自引率

12.10%

发文量

471

审稿时长

1.6 months

期刊介绍： Circulation publishes original research manuscripts, review articles, and other content related to cardiovascular health and disease, including observational studies, clinical trials, epidemiology, health services and outcomes studies, and advances in basic and translational research.