Application of Multigene Panel Sequencing in Patients with Prolonged Rate-corrected QT Interval and No Pathogenic Variants Detected in KCNQ1, KCNH2, and SCN5A

作者：Seo Soo Hyun; Kim So Yeon; Cho Sung Im; Park Hyunwoong; Lee Seungjun; Choi Jong Moon; Kim Man Jin; Lee Jee Soo; Ahn Kyung Jin; Song Mi Kyoung; Bae Eun Jung; Park Sung Sup; Seong Moon Woo^*

来源：Annals of Laboratory Medicine, 2018, 38(1): 54-+.

DOI：10.3343/alm.2018.38.1.54

• Multigene panel sequencing
• Prolonged heart rate-corrected QT interval
• Long QT syndrome

Long QT syndrome (LQTS) is an inherited cardiac disease characterized by a prolonged heart rate-corrected QT (QTc) interval. We investigated the genetic causes in patients with prolonged QTc intervals who were negative for pathogenic variants in three major LQTS-related genes (KCNQ1, KCNH2, and SCN5A). Molecular genetic testing was performed using a panel including 13 LQTS-related genes and 67 additional genes implicated in other cardiac diseases. Overall, putative genetic causes of prolonged QTc interval were identified in three of the 30 patients (10%). Among the LQTS-related genes, we detected a previously reported pathogenic variant, CACNA1C c. 1552C > T, responsible for cardiaconly Timothy syndrome. Among the genes related to other cardiac diseases, a likely pathogenic variant, RYR2 c. 11995A>G, was identified in a patient with catecholaminergic polymorphic ventricular tachycardia. Another patient who developed dilated cardiomyopathy with prolonged QTc interval was found to carry a likely pathogenic variant, TAZ c.718G>A, associated with infantile dilated cardiomyopathy. Comprehensive screening of genetic variants using multigene panel sequencing enables detection of genetic variants with a possible involvement in QTc interval prolongation, thus uncovering unknown molecular mechanisms underlying LQTS.

• 出版日期2018-1