Genotype-Phenotype Aspects of Type 2 Long QT Syndrome
Wataru Shimizu, MD, PhD*,*,
Arthur J. Moss, MD ,
Arthur A.M. Wilde, MD, PhD||,
Jeffrey A. Towbin, MD#,
Michael J. Ackerman, MD, PhD**,
Craig T. January, MD, PhD ,
David J. Tester, BS**,
Wojciech Zareba, MD, PhD,
Jennifer L. Robinson, MS,
Ming Qi, PhD ,
G. Michael Vincent, MD,
Elizabeth S. Kaufman, MD,
Nynke Hofman, MSc¶,
Takashi Noda, MD, PhD*,
Shiro Kamakura, MD, PhD*,
Yoshihiro Miyamoto, MD, PhD,
Samit Shah, BA,
Vinit Amin, MA,
Ilan Goldenberg, MD,
Mark L. Andrews, BBA and
Scott McNitt, MS
* Division of Cardiology, Department of Internal Medicine, National Cardiovascular Center, Suita, Osaka, Japan
Laboratory of Molecular Genetics, National Cardiovascular Center, Suita, Osaka, Japan
Cardiology Division, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York
Department of Pathology, University of Rochester School of Medicine and Dentistry, Rochester, New York
|| Department of Cardiology, Academic Medical Center, Amsterdam, the Netherlands
¶ Department of Clinical Genetics, Academic Medical Center, Amsterdam, the Netherlands
# Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas
** Departments of Medicine, Pediatrics, and Molecular Pharmacology, Mayo Clinic College of Medicine, Rochester, Minnesota
Departments of Medicine and Physiology, University of Wisconsin-Madison, Madison, Wisconsin
University of Utah, School of Medicine, Salt Lake City, Utah
Heart and Vascular Research Center, MetroHealth Campus of Case Western Reserve University, Cleveland, Ohio
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Figure 1 Location of Different Mutations in KCNH2 Potassium Channel
Diagramatic location of 162 different mutations in the KCNH2 potassium channel involving 858 subjects. The  subunit involves the N-terminus (NH3+), 6 membrane-spanning segments, and the C-terminus portion (COO–). The numbers in parentheses refer to the position of the amino acid beginning at the N-term position (1), the beginning of the transmembrane nonpore S1 to S4 sequence (398), the beginning of the transmembrane S5-loop-S6 sequence (552), the end of the transmembrane S6 sequence (657), and at the C-term end position (1,159). The open circles represent individual amino acids, the red circles indicate the missense mutations, and the blue circles indicate nonmissense mutations. The cylinders represent putative -helical segments, and the bars represent putative β-sheets.
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Figure 2 Kaplan-Meier Estimates of Cumulative Probability of First Cardiac Event
Kaplan-Meier estimate of the cumulative probability of a first cardiac event by (A) type, (B) location, and (C) topology of the mutation for all 858 subjects with genetically confirmed KCNH2 mutations. Kaplan-Meier estimate of the cumulative probability of a first cardiac event for (D) missense mutations within different locations and for (E) mutations located in the -helical domains within different locations. The numbers in parentheses reflect the cumulative event rate at that point in time.
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