Challenges in Molecular Diagnostics of Channelopathies in the Next-Generation Sequencing Era: Less Is More?

[摘要] Long QT syndrome (LQTS), Brugada syndrome (BrS), and catecholaminergic polymorphic ventricular tachycardia (CPVT) are the main channelopathies that can cause for sudden cardiac death (SCD) in children or young adults. In the last few years, the number of genes and genetic variants associated with these diseases has increased. For example, there are 15 known LQTS1 genes and at least 16 BrS genes.2 Importantly, however, in each disease, there are few major genes and a larger number of genes accounting for few cases each. The “minor” genes are usually poorly characterized in terms of function and pathophysiological role. As a consequence, the identification of mutations in these genes often leads to results that are difficult to interpret. Therefore, the HRS expert consensus statement on the diagnosis and management of patients with inherited arrhythmias syndromes (2) has outlined the indications for genetic testing on the basis of the epidemiological relevance of the genes and the clinical implications of genetic testing for each disease (i.e., how much the identification of the mutation can impact the clinical management).

[学科分类] 心脏病和心血管学

[关键词] genetic variants;next-generation sequencing;channelopathy genetic testing;genetic panel