Korean Circ J.  2023 Oct;53(10):693-707. 10.4070/kcj.2023.0083.

Clinical and Genetic Features of Korean Inherited Arrhythmia Probands

• Jeong JH
• Oh SK
• Kim YG
• Choi YY
• Lee HS
• Shim J
• Park YM
• Kim JH
• Oh YS
• Kim NH
• Pak HN
• On YK
• Park HW
• Hwang GS
• Kim DK
• Park YA
• Park HS
• Cho Y
• Oh S
• Choi JI
• Kim YH

• KMID: 2546993
• DOI: http://doi.org/10.4070/kcj.2023.0083

Abstract

Background and Objectives
Inherited arrhythmia (IA) is a more common cause of sudden cardiac death in Asian population, but little is known about the genetic background of Asian IA probands. We aimed to investigate the clinical characteristics and analyze the genetic underpinnings of IA in a Korean cohort.
Methods
This study was conducted in a multicenter cohort of the Korean IA Registry from 2014 to 2017. Genetic testing was performed using a next-generation sequencing panel including 174 causative genes of cardiovascular disease.
Results
Among the 265 IA probands, idiopathic ventricular fibrillation (IVF) and Brugada Syndrome (BrS) was the most prevalent diseases (96 and 95 cases respectively), followed by long QT syndrome (LQTS, n=54). Two-hundred-sixteen probands underwent genetic testing, and 69 probands (31.9%) were detected with genetic variant, with yield of pathogenic or likely pathogenic variant as 6.4%. Left ventricular ejection fraction was significantly lower in genotype positive probands (54.7±11.3 vs. 59.3±9.2%, p=0.005). IVF probands showed highest yield of positive genotype (54.0%), followed by LQTS (23.8%), and BrS (19.5%).
Conclusions
There were significant differences in clinical characteristics and genetic yields among BrS, LQTS, and IVF. Genetic testing did not provide better yield for BrS and LQTS. On the other hand, in IVF, genetic testing using multiple gene panel might enable the molecular diagnosis of concealed genotype, which may alter future clinical diagnosis and management strategies.

Keyword

Genetic testing; High-throughput nucleotide sequencing; Channelopathies; Cardiomyopathies

Figure

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  Figure 1 Study flow chart.P/LP = pathogenic or likely pathogenic.

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  Figure 2 Proportion of inherited arrhythmia in Korean probands.ARVC = arrhythmogenic right ventricular cardiomyopathy; BrS = Brugada syndrome; CPVT = catecholaminergic polymorphic ventricular tachycardia; ERS = early repolarization syndrome; IVF = idiopathic ventricular fibrillation; LQTS = long QT syndrome; SQTS = short QT syndrome.

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  Figure 3 Comparison of genetic characteristics between pathogenic or likely pathogenic and non-pathogenic variants. In-silico prediction was regarded as positive if more than half of the variants were predicted to have deleterious effects.P/LP = pathogenic or likely pathogenic.

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  Figure 4 Yield of genetic testing according to diagnosis.BrS = Brugada syndrome; IVF = idiopathic ventricular fibrillation; LQTS = long QT syndrome; P/LP = pathogenic or likely pathogenic.

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