(Circulation. 1997;95:565-567.)
© 1997 American Heart Association, Inc.
Articles |
Four Novel KVLQT1 and Four Novel HERG Mutations in Familial Long-QT Syndrome
the Laboratory of Molecular Medicine, Institute of Medical Science, University of Tokyo (T.T., Y.N.); Second Department of Internal Medicine, Gunma University School of Medicine (R.N.); First Department of Internal Medicine, Yamagata University School of Medicine (H.T.); First Department of Internal Medicine, School of Medicine, Kanazawa University (S.T.); Third Department of Internal Medicine, School of Medicine, Nagasaki University (K. Yano); Department of Pediatrics, School of Medicine, Juntendo University, Tokyo (K. Yabuta); Department of Pediatrics, Shimane Medical University (N.H.); Department of Pediatrics, Takamatsu Municipal Hospital, Kagawa (O.N.); First Department of Internal Medicine, School of Medicine, Niigata University (A.S.); Division of Cardiology, Department of Medicine, Kawasaki Medical School, Okayama (T.S.); Department of Cardiology, Metropolitan Kiyose Children's Hospital, Tokyo (H.K.); and Department of Internal Medicine III, University of Tokyo School of Medicine (Y.Y.), Japan.
Correspondence to Toshihiro Tanaka, MD, Laboratory of Molecular Medicine, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108, Japan. E-mail toshitan@ims.u-tokyo.ac.jp.
Background Familial long-QT syndrome (LQTS) is characterized by prolonged ventricular repolarization. Clinical symptoms include recurrent syncopal attacks, and sudden death may occur due to ventricular tachyarrhythmias. Three genes responsible for this syndrome (KVLQT1, HERG, and SCN5A) have been identified so far. We investigated mutations of these genes in LQTS families.
Methods and Results Thirty-two Japanese families with LQTS were brought together for screening for mutations. Genomic DNA from each proband was examined by the polymerase chain reaction–single-strand conformation polymorphism technique followed by direct DNA sequencing. In four of the families, comprising 16 patients, mutations were identified in KVLQT1; five other families (9 patients) segregated mutant alleles of HERG. All 25 of these patients carried the specific mutations present in their respective families, and none of 80 normal individuals carried these alleles. Mutations were confirmed by endonuclease digestion or hybridization of mutant allele–specific oligonucleotides. No mutation in SCN5A was found in any family.
Conclusions We identified nine different mutations among 32 families with LQTS. Eight of these were novel and account for 25% of all types of mutations reported to date. Such a variety of mutations makes it difficult to screen high-risk groups using simple methods such as endonuclease digestion or mutant allele–specific amplification.
Key Words: genes • intervals • genetics • death, sudden • torsade de pointes • tachyarrhythmia
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