Determination of Pathogenic Variants in Inherited Arrhythmia Syndromes and the Realization of Personalized Medicine Based on Genetic Information

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08075
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Kanazawa University
• Principal Investigator: Hayashi Kenshi 金沢大学, 保健学系, 准教授 (00422642)
• Co-Investigator(Kenkyū-buntansha): 吉田 昌平 金沢大学, 附属病院, 助教 (30623657) ; 野村 章洋 金沢大学, 附属病院, 特任准教授 (30707542) ; 藤野 陽 金沢大学, 保健学系, 教授 (40361993)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 遺伝性不整脈 / 遺伝性心筋症 / 遺伝子バリアント / 網羅的遺伝子解析 / ゼブラフィッシュ / 機能解析

Outline of Final Research Achievements

A comprehensive genetic analysis was performed using next-generation sequencing on 92 cases of congenital long QT syndrome (LQTS), 73 cases of dilated cardiomyopathy, 162 cases of hypertrophic cardiomyopathy, and 32 cases of early-onset conduction disorders, all of which are significant causes of sudden cardiac death. As a result, pathogenic variants were found in 115 out of 359 cases (32%).
In type 1 LQTS, about 30% of variants of uncertain significance were found in KCNQ1. To clarify their clinical significance, the role of the zebrafish cardiac arrhythmia model was investigated. It was revealed that this model is useful for determining the pathogenicity of loss-of-function mutations.

Free Research Field

循環器研究

Academic Significance and Societal Importance of the Research Achievements

我が国の心臓突然死の原疾患の約40％が遺伝性心筋症・不整脈であると考えられる。今回遺伝性心筋症・不整脈症例において約1/3の症例に病的バリアントを見出すことができた。病的意義不明のバリアントの病原性を判断するためにゼブラフィッシュ心臓不整脈モデルが有用と考えられた。バリアントの病的意義を明らかにすることで、バリアント情報に基づいた患者の管理・治療方針の決定が可能になると考えられる。