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Annals of Laboratory Medicine
Article . 2018 . Peer-reviewed
License: CC BY NC
Data sources: Crossref
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PubMed Central
Other literature type . 2018
License: CC BY NC
Data sources: PubMed Central
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Application of Multigene Panel Sequencing in Patients with Prolonged Rate-corrected QT Interval and No Pathogenic Variants Detected in KCNQ1, KCNH2, and SCN5A

Authors: Seo, Soo Hyun; Kim, So Yeon; Cho, Sung Im; Park, Hyunwoong; Lee, Seungjun; Choi, Jong-Moon; Kim, Man Jin; +6 Authors

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

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.

Keywords

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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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
5
Average
Average
Average
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gold