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Evaluation of genes encoding for the transient outward current (Ito) identifies the KCND2 gene as a cause of J-wave syndrome associated with sudden cardiac death.
Perrin, Mark J; Adler, Arnon; Green, Sharon; Al-Zoughool, Foad; Doroshenko, Petro; Orr, Nathan; Uppal, Shaheen; Healey, Jeff S; Birnie, David; Sanatani, Shubhayan; Gardner, Martin; Champagne, Jean; Simpson, Chris; Ahmad, Kamran; van den Berg, Maarten P; Chauhan, Vijay; Backx, Peter H; van Tintelen, J Peter; Krahn, Andrew D; Gollob, Michael H.
Afiliação
  • Perrin MJ; From the Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa (M.J.P., A.A., S.G., F.A.-Z., P.D., N.O., S.U., D.B.); Population Health Research Institute, McMaster University, Hamilton, ON (J.S.H.); Division of Cardiology, Department of Medicine, University of
  • Adler A; From the Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa (M.J.P., A.A., S.G., F.A.-Z., P.D., N.O., S.U., D.B.); Population Health Research Institute, McMaster University, Hamilton, ON (J.S.H.); Division of Cardiology, Department of Medicine, University of
  • Green S; From the Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa (M.J.P., A.A., S.G., F.A.-Z., P.D., N.O., S.U., D.B.); Population Health Research Institute, McMaster University, Hamilton, ON (J.S.H.); Division of Cardiology, Department of Medicine, University of
  • Al-Zoughool F; From the Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa (M.J.P., A.A., S.G., F.A.-Z., P.D., N.O., S.U., D.B.); Population Health Research Institute, McMaster University, Hamilton, ON (J.S.H.); Division of Cardiology, Department of Medicine, University of
  • Doroshenko P; From the Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa (M.J.P., A.A., S.G., F.A.-Z., P.D., N.O., S.U., D.B.); Population Health Research Institute, McMaster University, Hamilton, ON (J.S.H.); Division of Cardiology, Department of Medicine, University of
  • Orr N; From the Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa (M.J.P., A.A., S.G., F.A.-Z., P.D., N.O., S.U., D.B.); Population Health Research Institute, McMaster University, Hamilton, ON (J.S.H.); Division of Cardiology, Department of Medicine, University of
  • Uppal S; From the Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa (M.J.P., A.A., S.G., F.A.-Z., P.D., N.O., S.U., D.B.); Population Health Research Institute, McMaster University, Hamilton, ON (J.S.H.); Division of Cardiology, Department of Medicine, University of
  • Healey JS; From the Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa (M.J.P., A.A., S.G., F.A.-Z., P.D., N.O., S.U., D.B.); Population Health Research Institute, McMaster University, Hamilton, ON (J.S.H.); Division of Cardiology, Department of Medicine, University of
  • Birnie D; From the Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa (M.J.P., A.A., S.G., F.A.-Z., P.D., N.O., S.U., D.B.); Population Health Research Institute, McMaster University, Hamilton, ON (J.S.H.); Division of Cardiology, Department of Medicine, University of
  • Sanatani S; From the Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa (M.J.P., A.A., S.G., F.A.-Z., P.D., N.O., S.U., D.B.); Population Health Research Institute, McMaster University, Hamilton, ON (J.S.H.); Division of Cardiology, Department of Medicine, University of
  • Gardner M; From the Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa (M.J.P., A.A., S.G., F.A.-Z., P.D., N.O., S.U., D.B.); Population Health Research Institute, McMaster University, Hamilton, ON (J.S.H.); Division of Cardiology, Department of Medicine, University of
  • Champagne J; From the Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa (M.J.P., A.A., S.G., F.A.-Z., P.D., N.O., S.U., D.B.); Population Health Research Institute, McMaster University, Hamilton, ON (J.S.H.); Division of Cardiology, Department of Medicine, University of
  • Simpson C; From the Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa (M.J.P., A.A., S.G., F.A.-Z., P.D., N.O., S.U., D.B.); Population Health Research Institute, McMaster University, Hamilton, ON (J.S.H.); Division of Cardiology, Department of Medicine, University of
  • Ahmad K; From the Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa (M.J.P., A.A., S.G., F.A.-Z., P.D., N.O., S.U., D.B.); Population Health Research Institute, McMaster University, Hamilton, ON (J.S.H.); Division of Cardiology, Department of Medicine, University of
  • van den Berg MP; From the Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa (M.J.P., A.A., S.G., F.A.-Z., P.D., N.O., S.U., D.B.); Population Health Research Institute, McMaster University, Hamilton, ON (J.S.H.); Division of Cardiology, Department of Medicine, University of
  • Chauhan V; From the Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa (M.J.P., A.A., S.G., F.A.-Z., P.D., N.O., S.U., D.B.); Population Health Research Institute, McMaster University, Hamilton, ON (J.S.H.); Division of Cardiology, Department of Medicine, University of
  • Backx PH; From the Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa (M.J.P., A.A., S.G., F.A.-Z., P.D., N.O., S.U., D.B.); Population Health Research Institute, McMaster University, Hamilton, ON (J.S.H.); Division of Cardiology, Department of Medicine, University of
  • van Tintelen JP; From the Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa (M.J.P., A.A., S.G., F.A.-Z., P.D., N.O., S.U., D.B.); Population Health Research Institute, McMaster University, Hamilton, ON (J.S.H.); Division of Cardiology, Department of Medicine, University of
  • Krahn AD; From the Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa (M.J.P., A.A., S.G., F.A.-Z., P.D., N.O., S.U., D.B.); Population Health Research Institute, McMaster University, Hamilton, ON (J.S.H.); Division of Cardiology, Department of Medicine, University of
  • Gollob MH; From the Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa (M.J.P., A.A., S.G., F.A.-Z., P.D., N.O., S.U., D.B.); Population Health Research Institute, McMaster University, Hamilton, ON (J.S.H.); Division of Cardiology, Department of Medicine, University of
Circ Cardiovasc Genet ; 7(6): 782-9, 2014 Dec.
Article em En | MEDLINE | ID: mdl-25214526
ABSTRACT

BACKGROUND:

J-wave ECG patterns are associated with an increased risk of sudden arrhythmic death, and experimental evidence supports a transient outward current (I(to))-mediated mechanism of J-wave formation. This study aimed to determine the frequency of genetic mutations in genes encoding the I(to) in patients with J waves on ECG. METHODS AND

RESULTS:

Comprehensive mutational analysis was performed on I(to)-encoding KCNA4, KCND2, and KCND3 genes, as well as the previously described J-wave-associated KCNJ8 gene, in 51 unrelated patients with ECG evidence defining a J-wave syndrome. Only patients with a resuscitated cardiac arrest or type 1 Brugada ECG pattern were included for analysis. A rare genetic mutation of the KCND2 gene, p.D612N, was identified in a single patient. Co-expression of mutant and wild-type KCND2 with KChIP2 in HEK293 cells demonstrated a gain-of-function phenotype, including an increase in peak I(to) density of 48% (P<0.05) in the heterozygous state. Using computer modeling, this increase in Ito resulted in loss of the epicardial action potential dome, predicting an increased ventricular transmural Ito gradient. The previously described KCNJ8-S422L mutation was not identified in this cohort of patients with ECG evidence of J-wave syndrome.

CONCLUSIONS:

These findings are the first to implicate the KCND2 gene as a novel cause of J-wave syndrome associated with sudden cardiac arrest. However, genetic defects in I(to)-encoding genes seem to be an uncommon cause of sudden cardiac arrest in patients with apparent J-wave syndromes.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Morte Súbita Cardíaca / Canais de Potássio Shal / Síndrome de Brugada Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Adult / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Circ Cardiovasc Genet Ano de publicação: 2014 Tipo de documento: Article
Texto completo
Imprimir
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PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Morte Súbita Cardíaca / Canais de Potássio Shal / Síndrome de Brugada Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Adult / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Circ Cardiovasc Genet Ano de publicação: 2014 Tipo de documento: Article