A research for the diagnosis of RYR2-positive LQTS and its arrhythmogenicity

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17146
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Fujii Yusuke 滋賀医科大学, 医学部, 助教 (10837868)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: RYR2 / CALM / CPVT / LQTS

Outline of Final Research Achievements

Initially, we planned to compare CPVT1 patients with QT prolongation with LQTS patients. However, because of the insufficient patient number, we extended our analysis to CPVT2(CALM) patients and CALM related LQTS patients. By the analysis of CALM-LQTS patients, we found 6 variants in 9 patients Among 322 children in calmodulin-encoded genes (2.8%) Their clinical diagnoses were LQTS (n=4), CPVT (n=3), and both (n=2). Their age of diagnosis ranges at 0-9 with the median of 5 years. There were three major clinical phenotypes; 1) CALM2-D96V, and E141K: two infants with advanced atrio-ventricular block, significant QTc prolongation, severe heart failure from their fetal period; both of them deceased within 1.5-year-old. Their phenotypes seemed to be mutation specific. Their cardiac features were severer, and the onset of LAEs was earlier compared with other genotypes of LQTS/CPVT.
We reported these findings in the scientific meeting, European Society of Cardiology 2022.

Free Research Field

Genetic arrhythmia

Academic Significance and Societal Importance of the Research Achievements

CPVT/ CALM関連LQTSは重症度の高い遺伝性不整脈疾患であるが、その頻度が少ないこともあり、特にCPVTに対しての遺伝子検査が保険適応となっていないなど、医療における対応はいまだ発展途上である。本研究を通して、国内におけるCPVT, CALM関連LQTSの病態についてより理解が進むことが期待される。特に、乳幼児期に致死性不整脈が多いという知見は重要なメッセージであり、これらのエビデンスを国内症例で蓄積することで、今後のCPVTに遺伝子検査保険適応導入などのアウトカムにつなげていけることが期待される。