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Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death

Publication ,  Journal Article
Burashnikov, E; Pfeiffer, R; Barajas-Martinez, H; Delpn, E; Hu, D; Desai, M; Borggrefe, M; Hissaguerre, M; Kanter, R; Pollevick, GD; Laio, R ...
Published in: Heart Rhythm
2010

Background L-type calcium channel (LTCC) mutations have been associated with Brugada syndrome (BrS), short QT (SQT) syndrome, and Timothy syndrome (LQT8). Little is known about the extent to which LTCC mutations contribute to the J-wave syndromes associated with sudden cardiac death. Objective The purpose of this study was to identify mutations in the α1, β2, and α2δ subunits of LTCC (Cav1.2) among 205 probands diagnosed with BrS, idiopathic ventricular fibrillation (IVF), and early repolarization syndrome (ERS). CACNA1C, CACNB2b, and CACNA2D1 genes of 162 probands with BrS and BrS+SQT, 19 with IVF, and 24 with ERS were screened by direct sequencing. Methods/Results Overall, 23 distinct mutations were identified. A total of 12.3%, 5.2%, and 16% of BrS/BrS+SQT, IVF, and ERS probands displayed mutations in α1, β2, and α2δ subunits of LTCC, respectively. When rare polymorphisms were included, the yield increased to 17.9%, 21%, and 29.1% for BrS/BrS+SQT, IVF, and ERS probands, respectively. Functional expression of two CACNA1C mutations associated with BrS and BrS+SQT led to loss of function in calcium channel current. BrS probands displaying a normal QTc had additional variations known to prolong the QT interval. Conclusion The study results indicate that mutations in the LTCCs are detected in a high percentage of probands with J-wave syndromes associated with inherited cardiac arrhythmias, suggesting that genetic screening of Ca v genes may be a valuable diagnostic tool in identifying individuals at risk. These results are the first to identify CACNA2D1 as a novel BrS susceptibility gene and CACNA1C, CACNB2, and CACNA2D1 as possible novel ERS susceptibility genes. © 2010 Heart Rhythm Society.

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Published In

Heart Rhythm

DOI

ISSN

1547-5271

Publication Date

2010

Volume

7

Issue

12

Start / End Page

1872 / 1882

Related Subject Headings

  • Cardiovascular System & Hematology
  • 1102 Cardiorespiratory Medicine and Haematology
  • 0903 Biomedical Engineering
 

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Burashnikov, E., Pfeiffer, R., Barajas-Martinez, H., Delpn, E., Hu, D., Desai, M., … Antzelevitch, C. (2010). Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death. Heart Rhythm, 7(12), 1872–1882. https://doi.org/10.1016/j.hrthm.2010.08.026
Burashnikov, E., R. Pfeiffer, H. Barajas-Martinez, E. Delpn, D. Hu, M. Desai, M. Borggrefe, et al. “Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death.” Heart Rhythm 7, no. 12 (2010): 1872–82. https://doi.org/10.1016/j.hrthm.2010.08.026.
Burashnikov E, Pfeiffer R, Barajas-Martinez H, Delpn E, Hu D, Desai M, et al. Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death. Heart Rhythm. 2010;7(12):1872–82.
Burashnikov, E., et al. “Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death.” Heart Rhythm, vol. 7, no. 12, 2010, pp. 1872–82. Scival, doi:10.1016/j.hrthm.2010.08.026.
Burashnikov E, Pfeiffer R, Barajas-Martinez H, Delpn E, Hu D, Desai M, Borggrefe M, Hissaguerre M, Kanter R, Pollevick GD, Guerchicoff A, Laio R, Marieb M, Nademanee K, Nam GB, Robles R, Schimpf R, Stapleton DD, Viskin S, Winters S, Wolpert C, Zimmern S, Veltmann C, Antzelevitch C. Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death. Heart Rhythm. 2010;7(12):1872–1882.
Journal cover image

Published In

Heart Rhythm

DOI

ISSN

1547-5271

Publication Date

2010

Volume

7

Issue

12

Start / End Page

1872 / 1882

Related Subject Headings

  • Cardiovascular System & Hematology
  • 1102 Cardiorespiratory Medicine and Haematology
  • 0903 Biomedical Engineering