Application of Multigene Panel Sequencing in Patients with Prolonged Rate-corrected QT Interval and No Pathogenic Variants Detected in KCNQ1, KCNH2, and SCN5A
- Author:
Soo Hyun SEO
1
;
So Yeon KIM
;
Sung Im CHO
;
Hyunwoong PARK
;
Seungjun LEE
;
Jong Moon CHOI
;
Man Jin KIM
;
Jee Soo LEE
;
Kyung Jin AHN
;
Mi Kyoung SONG
;
Eun Jung BAE
;
Sung Sup PARK
;
Moon Woo SEONG
Author Information
- Publication Type:Brief Communication
- Keywords: Multigene panel sequencing; Prolonged heart rate-corrected QT interval; Long QT syndrome
- MeSH: Cardiomyopathy, Dilated; Heart; Heart Diseases; Humans; Long QT Syndrome; Mass Screening; Molecular Biology; Ryanodine Receptor Calcium Release Channel; Tachycardia, Ventricular
- From:Annals of Laboratory Medicine 2018;38(1):54-58
- CountryRepublic of Korea
- Language:English
- Abstract: 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.
