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Human Genetics

, Volume 102, Issue 4, pp 435–439 | Cite as

Genomic organization and mutational analysis of HERG, a gene responsible for familial long QT syndrome

  • Toshio Itoh
  • T. Tanaka
  • Ryozo Nagai
  • Tetsuro Kamiya
  • Toshitami Sawayama
  • Toshio Nakayama
  • Hitonobu Tomoike
  • Harumizu Sakurada
  • Yoshio Yazaki
  • Yusuke Nakamura
Original investigation

Abstract

Familial long QT syndrome (LQTS) is characterized by prolonged ventricular repolarization. Clinical symptoms include recurrent syncopal attacks, and sudden death may occur as a result of ventricular tachyarrhythmias. Three genes responsible for this syndrome (KVLQT1, HERG, and SCN5A) have been identified so far, and mutations have been reported on the basis of partially characterized genomic organization. To optimize the search for HERG mutations, we have determined the genomic structure of HERG and investigated mutations in LQTS families. Human genomic clones containing the HERG gene were isolated from a human genomic library by using reverse-transcribed polymerase chain reaction (RT-PCR) products from this gene as probes. We determined exon/intron boundaries and flanking intronic sequences by using primers synthesized on the basis of the HERG cDNA sequence available in the DNA database. HERG was shown to consist of 15 exons spanning approximately 19 kb on chromosome 7q35. Subsequently, we synthesized oligonucleotide primers to cover the entire coding region and searched for mutations in 36 Japanese LQTS families. When genomic DNA from each proband was examined by the PCR/single-strand conformation polymorphism technique followed by direct DNA sequencing, five novel mutations were detected. Each mutation was present in affected relatives of the respective proband. This work should increase the efficiency of screening mutations associated with HERG.

Keywords

Genomic Organization Ventricular Tachyarrhythmia Entire Code Region Ventricular Repolarization Affected Relative 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Toshio Itoh
    • 1
  • T. Tanaka
    • 1
  • Ryozo Nagai
    • 2
  • Tetsuro Kamiya
    • 3
  • Toshitami Sawayama
    • 4
  • Toshio Nakayama
    • 5
  • Hitonobu Tomoike
    • 6
  • Harumizu Sakurada
    • 7
  • Yoshio Yazaki
    • 8
  • Yusuke Nakamura
    • 1
  1. 1.Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6–1, Shirokanedai, Minato-ku, Tokyo 108, Japan Tel.: +81-35449-5374, Fax: +81-35449-5406, e-mail: toshitan@ims.u-tokyo.ac.jpJP
  2. 2.Second Department of Internal Medicine, Gunma University School of Medicine, Gunma, JapanJP
  3. 3.Department of Pediatrics, National Cardiovascular Center, Osaka, JapanJP
  4. 4.Division of Cardiology, Department of Medicine, Kawasaki Medical School, Okayama, JapanJP
  5. 5.Department of Cardiology, Jichi Medical School, Tochigi, JapanJP
  6. 6.First Department of Internal Medicine, Yamagata University, School of Medicine, Yamagata, JapanJP
  7. 7.Division of Cardiology, Metropolitan Hiroo Hospital, Tokyo, JapanJP
  8. 8.Department of Internal Medicine III, University of Tokyo School of Medicine, Tokyo, JapanJP

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