Get access

A Missense Mutation in the Sodium Channel β2 Subunit Reveals SCN2B as a New Candidate Gene for Brugada Syndrome

Authors

  • Helena Riuró,

    1. Cardiovascular Genetics Center, Institut d'Investigació Biomèdica de Girona (IDIBGI), Girona, Spain
    2. Department of Medical Science, Medical School, Universitat de Girona (UdG), Girona, Spain
    Search for more papers by this author
  • Pedro Beltran-Alvarez,

    1. Cardiovascular Genetics Center, Institut d'Investigació Biomèdica de Girona (IDIBGI), Girona, Spain
    2. Department of Medical Science, Medical School, Universitat de Girona (UdG), Girona, Spain
    Search for more papers by this author
  • Anna Tarradas,

    1. Cardiovascular Genetics Center, Institut d'Investigació Biomèdica de Girona (IDIBGI), Girona, Spain
    2. Department of Medical Science, Medical School, Universitat de Girona (UdG), Girona, Spain
    Search for more papers by this author
  • Elisabet Selga,

    1. Cardiovascular Genetics Center, Institut d'Investigació Biomèdica de Girona (IDIBGI), Girona, Spain
    2. Department of Medical Science, Medical School, Universitat de Girona (UdG), Girona, Spain
    Search for more papers by this author
  • Oscar Campuzano,

    1. Cardiovascular Genetics Center, Institut d'Investigació Biomèdica de Girona (IDIBGI), Girona, Spain
    2. Department of Medical Science, Medical School, Universitat de Girona (UdG), Girona, Spain
    Search for more papers by this author
  • Marcel Vergés,

    1. Cardiovascular Genetics Center, Institut d'Investigació Biomèdica de Girona (IDIBGI), Girona, Spain
    2. Department of Medical Science, Medical School, Universitat de Girona (UdG), Girona, Spain
    Search for more papers by this author
  • Sara Pagans,

    1. Cardiovascular Genetics Center, Institut d'Investigació Biomèdica de Girona (IDIBGI), Girona, Spain
    2. Department of Medical Science, Medical School, Universitat de Girona (UdG), Girona, Spain
    Search for more papers by this author
  • Anna Iglesias,

    1. Cardiovascular Genetics Center, Institut d'Investigació Biomèdica de Girona (IDIBGI), Girona, Spain
    2. Department of Medical Science, Medical School, Universitat de Girona (UdG), Girona, Spain
    Search for more papers by this author
  • Josep Brugada,

    1. Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain
    Search for more papers by this author
  • Pedro Brugada,

    1. Heart Rhythm Management Centre, UZB, Brussels, Belgium
    Search for more papers by this author
  • Francisco M. Vázquez,

    1. Servicio de Cardiología, Hospital Virgen del Rocio, Sevilla, Spain
    Search for more papers by this author
  • Guillermo J. Pérez,

    1. Cardiovascular Genetics Center, Institut d'Investigació Biomèdica de Girona (IDIBGI), Girona, Spain
    2. Department of Medical Science, Medical School, Universitat de Girona (UdG), Girona, Spain
    Search for more papers by this author
  • Fabiana S. Scornik,

    1. Cardiovascular Genetics Center, Institut d'Investigació Biomèdica de Girona (IDIBGI), Girona, Spain
    2. Department of Medical Science, Medical School, Universitat de Girona (UdG), Girona, Spain
    Search for more papers by this author
    • These authors contributed equally to this work.

  • Ramon Brugada

    Corresponding author
    1. Cardiovascular Genetics Center, Institut d'Investigació Biomèdica de Girona (IDIBGI), Girona, Spain
    2. Department of Medical Science, Medical School, Universitat de Girona (UdG), Girona, Spain
    • Correspondence to: Ramon Brugada, Director Cardiovascular Genetics Center, IDIBGi-UdG, Parc Científic i Tecnològic, Edifici Giroemprèn A1.14–15. C/ Pic de Peguera, 11–15, 17003, Girona, Spain. E-mail: rbrugada@idibgi.org

    Search for more papers by this author
    • These authors contributed equally to this work.


  • Communicated by Michel Goossens

  • Contract grant sponsors: Instituto de Salud Carlos III (FI09/00336, CD09/00055, CD10/00275, CD11/00063 and PI2008/1800); Universitat de Girona (BR2012/47); CNIC-Translational 2008 (CNIC-03-2008); The Spanish Ministry of Health [Red Cooperativa de Insuficiencia Cardiaca (REDINSCOR) RD06/03/0018]; Sociedad Española de Cardiología (2011, Investigación Básica); Obra Social “La Caixa”.

ABSTRACT

Brugada Syndrome (BrS) is a familial disease associated with sudden cardiac death. A 20%–25% of BrS patients carry genetic defects that cause loss-of-function of the voltage-gated cardiac sodium channel. Thus, 70%–75% of patients remain without a genetic diagnosis. In this work, we identified a novel missense mutation (p.Asp211Gly) in the sodium β2 subunit encoded by SCN2B, in a woman diagnosed with BrS. We studied the sodium current (INa) from cells coexpressing Nav1.5 and wild-type (β2WT) or mutant (β2D211G) β2 subunits. Our electrophysiological analysis showed a 39.4% reduction in INa density when Nav1.5 was coexpressed with the β2D211G. Single channel analysis showed that the mutation did not affect the Nav1.5 unitary channel conductance. Instead, protein membrane detection experiments suggested that β2D211G decreases Nav1.5 cell surface expression. The effect of the mutant β2 subunit on the INa strongly suggests that SCN2B is a new candidate gene associated with BrS.

Ancillary