一个家族中的新型 RYR2 E4107A 变体的多种表型表现

IF 1.2 4区 医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS
Hiroshi Hasegawa, Shuntaro Tamura, Tadashi Nakajima, Reika Kawabata-Iwakawa, Takashi Kobari, Naohiro Matsumoto, Yukie Sano, Masahiko Nishiyama, Masahiko Kurabayashi, Yoshiaki Kaneko, Yosuke Nakatani, Hideki Ishii
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引用次数: 0

摘要

心脏雷诺丁受体(RyR2)功能增益突变会导致儿茶酚胺能多形性室性心动过速(CPVT)。相反,RyR2 功能缺失突变会导致一种新的疾病,称为钙释放缺乏综合征(CRDS),其中可能包括与 RYR2 相关的长 QT 综合征(LQTS)。重要的是,与 CPVT 不同,CRDS 患者并不总是表现出运动或肾上腺素诱发的室性心律失常,这就排除了 CRDS 的诊断。在此,我们报告了一名男孩和他的父亲,他们都经历过运动诱发的心脏事件,并携带相同的 RYR2 E4107A 变异。在这名男孩身上,运动负荷试验(EST)和肾上腺素激发试验(EPT)没有诱发任何室性心律失常。QTc略有延长(QTc:474毫秒),EPT引起QTc延长(QTc-基线:466毫秒,峰值:532毫秒,稳态:527毫秒)。相比之下,他父亲的 QTc 没有延长(QTc:417 毫秒),EST 和 EPT 均未诱发 QTc 延长。然而,EST 会诱发多灶性室性早搏(PVC)重影和双向 PVC 偶联。因此,他们表现出不同的临床表型:男孩表现出 LQTS(或 CRDS)表型,而父亲则表现出 CPVT 表型。这些研究结果表明,除了 RyR2 功能的改变外,其他未确定的因素,如其他遗传、表观遗传和环境因素以及衰老,也可能与不同的表型表现有关。考虑到单个 RYR2 变异可同时导致 CPVT 和 LQTS(或 CRDS)表型,在对 CPVT 和 CRDS 患者进行级联筛查时,仅有 EST 和 EPT 是不够的,还需要进行基因分析,以确定哪些人患危及生命的心律失常的风险会增加。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Diverse Phenotypic Manifestations in a Family with a Novel RYR2 E4107A Variant

Cardiac ryanodine receptor (RyR2) gain-of-function mutations cause catecholaminergic polymorphic ventricular tachycardia (CPVT). Conversely, RyR2 loss-of-function mutations cause a new disease entity, termed calcium release deficiency syndrome (CRDS), which may include RYR2-related long QT syndrome (LQTS). Importantly, unlike CPVT, patients with CRDS do not always exhibit exercise- or epinephrine-induced ventricular arrhythmias, which precludes a diagnosis of CRDS. Here we report a boy and his father, who both experienced exercise-induced cardiac events and harbor the same RYR2 E4107A variant. In the boy, an exercise stress test (EST) and epinephrine provocation test (EPT) did not induce any ventricular arrhythmias. QTc was slightly prolonged (QTc: 474 ms), and an EPT induced QTc prolongation (QTc-baseline: 466 ms, peak: 532 ms, steady-state: 527 ms). In contrast, in his father, QTc was not prolonged (QTc: 417 ms), and neither an EST nor EPT induced QTc prolongation. However, an EST induced multifocal premature ventricular contraction (PVC) bigeminy and bidirectional PVC couplets. Thus, they exhibited distinct clinical phenotypes: the boy exhibited LQTS (or CRDS) phenotype, whereas his father exhibited CPVT phenotype. These findings suggest that, in addition to the altered RyR2 function, other unidentified factors, such as other genetic, epigenetic, and environmental factors, and aging, may be involved in the diverse phenotypic manifestations. Considering that a single RYR2 variant can cause both CPVT and LQTS (or CRDS) phenotypes, in cascade screening of patients with CPVT and CRDS, an EST and EPT are not sufficient and genetic analysis is required to identify individuals who are at increased risk for life-threatening arrhythmias.

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来源期刊
International heart journal
International heart journal 医学-心血管系统
CiteScore
2.50
自引率
6.70%
发文量
148
审稿时长
6-12 weeks
期刊介绍: Authors of research articles should disclose at the time of submission any financial arrangement they may have with a company whose product figures prominently in the submitted manuscript or with a company making a competing product. Such information will be held in confidence while the paper is under review and will not influence the editorial decision, but if the article is accepted for publication, the editors will usually discuss with the authors the manner in which such information is to be communicated to the reader.
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