Exploratory research of causal genes by whole-exome sequencing in patients with familial WPW syndrome

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08319
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Nagoya University
• Principal Investigator: FUKASAWA YOSHIE 名古屋大学, 医学部附属病院, 病院助教 (00612764)
• Co-Investigator(Kenkyū-buntansha): 加藤 太一 名古屋大学, 医学系研究科, 准教授 (20422777)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: WPW症候群 / PRKAG2遺伝子 / エクソーム解析

Outline of Final Research Achievements

We conducted search for causal genes in 8 families with familial WPW syndrome by whole-exome sequencing. Only one family identified a pathogenic variant of PRKAG2 gene, already known as the causal gene of familial WPW syndrome. A missense mutation in a causal gene(gene X) of hypertrophic cardiomyopathy was confirmed in one family with WPW syndrome for more than 3 generations. There was no report of WPW syndrome caused by this gene variant, it was considered to be a novel phenotype. The causal gene couldn't detect in the other 6 families.
We planned an experimental functional analysis to prove that the pathogenic variant of gene X presents with WPW syndrome. We planned to create a model mouse using CRISPER-Cas9 and detect supraventricullar tachycardia caused by WPW syndrome with an implantable electrocardiograph, but we couldn't realize due to equipment and financial problems.

Free Research Field

小児循環器分野

Academic Significance and Societal Importance of the Research Achievements

「家族性WPW症候群の原因遺伝子＝PRKAG2」として知られているが、意外にもPRKAG2遺伝子の病的バリアントを有する確率は低いことが示された。また、PRKAG2遺伝子変異でもWPW症候群と肥大型心筋症と合併することが多いと報告されているが、この度確認された遺伝子Xについても肥大型心筋症の原因遺伝子であり、両疾患の発症には共通する分子メカニズムが存在する可能性が示唆された。