Application of Multigene Panel Sequencing in Patients with Prolonged Rate-corrected QT Interval and No Pathogenic Variants Detected in KCNQ1, KCNH2, and SCN5A
Application of Multigene Panel Sequencing in Patients with Prolonged Rate-corrected QT Interval and No Pathogenic Variants Detected in KCNQ1, KCNH2, and SCN5A
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.
- Seoul National University Korea (Republic of)
- Hallym University Sacred Heart Hospital Korea (Republic of)
- Sungkyunkwan University Korea (Republic of)
- Green Cross Laboratories (South Korea) Korea (Republic of)
- Gyeongsang National University Korea (Republic of)
Adult, Cardiomyopathy, Dilated, ERG1 Potassium Channel, Adolescent, Calcium Channels, L-Type, Genetic Variation, Infant, Ryanodine Receptor Calcium Release Channel, Brief Communication, Polymorphism, Single Nucleotide, NAV1.5 Voltage-Gated Sodium Channel, Electrocardiography, Long QT Syndrome, Child, Preschool, KCNQ1 Potassium Channel, Humans, Genetic Testing, Syndactyly, Autistic Disorder, Child, Acyltransferases
Adult, Cardiomyopathy, Dilated, ERG1 Potassium Channel, Adolescent, Calcium Channels, L-Type, Genetic Variation, Infant, Ryanodine Receptor Calcium Release Channel, Brief Communication, Polymorphism, Single Nucleotide, NAV1.5 Voltage-Gated Sodium Channel, Electrocardiography, Long QT Syndrome, Child, Preschool, KCNQ1 Potassium Channel, Humans, Genetic Testing, Syndactyly, Autistic Disorder, Child, Acyltransferases
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