Use of mutant-specific ion channel characteristics for risk stratification of long QT syndrome patients

Science Translational Medicine

Volumn 3, Issue 76, 2011, Pages

  Jons, Christian ^a   O Uchi, Jin ^a   Moss, Arthur J ^a   Reumann, Matthias ^b   Rice, John J ^b   Goldenberg, Ilan ^b   Zareba, Wojciech ^a   Wilde, Arthur A M ^c   Shimizu, Wataru ^d   Kanters, Jorgen K ^e,f   McNitt, Scott ^a   Hofman, Nynke ^c   Robinson, Jennifer L ^a   Lopes, Coeli M B ^a  

^a UNIVERSITY OF ROCHESTER SCHOOL OF MEDICINE AND DENTISTRY   (United States)

^b IBM T J WATSON RESEARCH CENTER   (United States)

^c UNIVERSITY OF AMSTERDAM   (Netherlands)

^d NATIONAL CEREBRAL AND CARDIOVASCULAR CENTER   (Japan)

^e GENTOFTE UNIVERSITY HOSPITAL   (Denmark)

^f DANISH NATIONAL RESEARCH FOUNDATION   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

POTASSIUM CHANNEL KCNQ1;

ANIMAL CELL; ARTICLE; CARDIOVASCULAR RISK; CELL ACTIVITY; COMPUTER MODEL; CONTROLLED STUDY; FEMALE; GENE ACTIVATION; GENE MUTATION; GENETIC ASSOCIATION; HEART ARREST; HEART BEAT; HEART DEPOLARIZATION; HEART MUSCLE FIBER MEMBRANE POTENTIAL; HETEROZYGOTE; HUMAN; HUMAN CELL; LONG QT SYNDROME; MAJOR CLINICAL STUDY; MALE; MATHEMATICAL MODEL; MISSENSE MUTATION; MUTATIONAL ANALYSIS; NONHUMAN; PHENOTYPE; POTASSIUM CURRENT; PREDICTION; PRIORITY JOURNAL; QT INTERVAL; RISK ASSESSMENT; RISK FACTOR; SUDDEN DEATH; SYNCOPE; ADOLESCENT; ADULT; ANIMAL; BIOLOGICAL MODEL; CHANNEL GATING; CHILD; COMPUTER SIMULATION; CYTOLOGY; ELECTROPHYSIOLOGY; GENETIC PREDISPOSITION; GENETICS; GENOTYPE; INFANT; KAPLAN MEIER METHOD; METABOLISM; MUTATION; OOCYTE; PATHOPHYSIOLOGY; PHYSIOLOGY; PRESCHOOL CHILD; PROPORTIONAL HAZARDS MODEL; REGISTER; XENOPUS LAEVIS;

ADOLESCENT; ADULT; ANIMALS; CHILD; CHILD, PRESCHOOL; COMPUTER SIMULATION; ELECTROPHYSIOLOGY; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; HUMANS; INFANT; ION CHANNEL GATING; KAPLAN-MEIER ESTIMATE; KCNQ1 POTASSIUM CHANNEL; LONG QT SYNDROME; MALE; MODELS, BIOLOGICAL; MUTATION; OOCYTES; PHENOTYPE; PROPORTIONAL HAZARDS MODELS; REGISTRIES; RISK FACTORS; XENOPUS LAEVIS; YOUNG ADULT;

EID: 79953240326     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3001551     Document Type: Article

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58. Acknowledgments: We thank J. Sorenson for her technical support. Funding: This work was supported by NIH R01(HL033843) and Mirowski-Moss Career Development Award at the University of Rochester Medical Center, Rochester (to C.J.); AHA Postdoctoral Fellowship (09POST2310079) (J.O.-U.); and Foreign Study Grant Award of Kanae Foundation (J.O.-U.). Author contributions: C.J. and J.O.-U. performed the experiments and data analysis and wrote the paper; C.M.B.L. guided the design of experiments and analysis; W.Z., A.A.M.W., W.S., J.K.K., and N.H. provided clinical data and contributed to analysis interpretation; A.J.M., I.G., S.M., and J.L.R. performed clinical data analysis and contributed to analysis interpretation; M.R. and J.J.R. performed computer simulation. Competing interests: A.A.M.W. is a member of the Advisory Board of PGxHealth. I.G. has been a paid consultant for Boston Scientific. The other authors declare that they have no competing interests.