title: Considerations when using next-generation sequencing for genetic diagnosis of long-QT syndrome in the clinical testing laboratory.
abstract: BACKGROUND
  Congenital long-QT syndrome (LQTS) is a potentially lethal cardiac electrophysiologic disorder characterized by QT interval prolongation and T-wave abnormalities. At least 13 LQTS-associated genes have been reported, but the high cost and low throughput of conventional Sanger sequencing has hampered the multi-gene-based LQTS diagnosis in clinical laboratories.
  
  
  METHODS
  We developed an NGS (next-generation sequencing)-based targeted gene panel for 13 LQTS genes using the Ion PGM platform, and a cohort of 36 LQTS patients were studied for characterization of analytical performance specifications.
  
  
  RESULTS
  This panel efficiently explored 212 of all 221 coding exons in 13 LQTS-associated genes. And for those genomic regions covered by the design of the NGS panel, the analytical sensitivity and analytical specificity for all potentially pathogenic variants were both 100% and showed 100% concordance with clinically validated Sanger sequencing results in five major LQTS genes (KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2).
  
  
  CONCLUSIONS
  This is the first description of an NGS panel targeting a multi-gene panel of 13 LQTS-associated genes. We developed and validated this robust, high-throughput NGS test and informatics pipeline for LQTS diagnosis suitable for the clinical testing laboratory.
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Hyojin
authors.initials: H
authors.lastname: Chae
authors.affiliation: Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Gun Dong
authors.initials: GD
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Woori
authors.initials: W
authors.lastname: Jang
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Joonhong
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Jekarl
authors.affiliation: Division of Cardiology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: oys@catholic.ac.kr.
authors.forename: Yong Seog
authors.initials: YS
authors.lastname: Oh
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: microkim@catholic.ac.kr.
authors.forename: Myungshin
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Yonggoo
authors.initials: Y
authors.lastname: Kim
mesh_terms: D000328:Adult; D019411:Clinical Laboratory Techniques; D005260:Female; D014644:Genetic Variation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008133:Long QT Syndrome / Q000151:congenital / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged
keywords: High-throughput nucleotide sequencing; Jervell–Lange Nielsen syndrome; Long-QT syndrome; Romano–Ward syndrome