Ann Lab Med 2018; 38(1): 54-58  
Application of Multigene Panel Sequencing in Patients with Prolonged Rate-corrected QT Interval and No Pathogenic Variants Detected in KCNQ1, KCNH2, and SCN5A
Soo Hyun Seo, M.D.1, So Yeon Kim, M.D.2, Sung Im Cho, M.T.3, Hyunwoong Park, M.D.4, Seungjun Lee, M.D.5, Jong-Moon Choi, M.D.6,7, Man Jin Kim, M.D.3, Jee-Soo Lee, M.D.8, Kyung Jin Ahn, M.D.9, Mi Kyoung Song, M.D.9, Eun-Jung Bae, M.D.9, Sung Sup Park, M.D.3, and Moon-Woo Seong, M.D.3
Department of Laboratory Medicine1, Seoul National University Bundang Hospital, Seongnam; Department of Laboratory Medicine2, National Medical Center, Seoul; Department of Laboratory Medicine3, Seoul National University Hospital, Seoul National University College of Medicine, Seoul; Department of Laboratory Medicine4, Gyeongsang National University Changwon Hospital, Changwon; Department of Laboratory Medicine5, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul; Green Cross Genome6, Yongin; Green Cross Laboratories7, Yongin; Department of Laboratory Medicine8, Hallym University Sacred Heart Hospital, Anyang; Department of Pediatrics9, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, Korea
Correspondence to: Moon-Woo Seong
Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea
Tel: +82-2-2072-4180
Fax: +82-2-747-0359
Received: March 23, 2017; Revised: June 29, 2017; Accepted: September 14, 2017; Published online: January 1, 2018.
© The Korean Society for Laboratory Medicine. All rights reserved.

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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 cardiac-only 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.
Keywords: Multigene panel sequencing, Prolonged heart rate-corrected QT interval, Long QT syndrome

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