Biophysical characterization of a new SCN5A mutation S1333Y in a SIDS infant linked to long QT syndrome

Huang, Hai; Millat, Gilles; Rodriguez-Lafrasse, Claire; Rousson, Robert; Kugener, Béatrice; Chevalier, Philippe; Chahine, Mohamed

doi:10.1016/j.febslet.2009.02.007

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Volume 583, Issue 5 , Pages 890-896, 4 March 2009

Biophysical characterization of a new SCN5A mutation S1333Y in a SIDS infant linked to long QT syndrome

Edited by Maurice Montal

Hai Huang
- Le Centre de Recherche Université Laval Robert-Giffard, Local F-6539, 2601 Chemin de la Canardière, Québec City, QC, Canada G1J 2G3
Gilles Millat
- Laboratoire de Biochimie et Biologie Moléculaire, Hôpital Cardiovasculaire et Pneumologique L Pradel, F-69677 Bron Cedex, France
Claire Rodriguez-Lafrasse
- Laboratoire de Biochimie et Biologie Moléculaire, Hôpital Cardiovasculaire et Pneumologique L Pradel, F-69677 Bron Cedex, France
Robert Rousson
- Laboratoire de Biochimie et Biologie Moléculaire, Hôpital Cardiovasculaire et Pneumologique L Pradel, F-69677 Bron Cedex, France
Béatrice Kugener
- Unité de Neuro-pédiatrie, Hôpital Debrousse, Lyon, France
Philippe Chevalier
- Unité de Cardiologie et Soins Intensifs, Hôpital Cardiovasculaire et Pneumologique L Pradel, F-69677 Bron Cedex, France
Mohamed Chahine
- Le Centre de Recherche Université Laval Robert-Giffard, Local F-6539, 2601 Chemin de la Canardière, Québec City, QC, Canada G1J 2G3
- Departement de Médecine, Université Laval, Québec City, QC, Canada G1K 7P4
- Corresponding author. Address: Le Centre de Recherche Université Laval Robert-Giffard, Local F-6539, 2601 Chemin de la Canardière, Québec City, QC, Canada G1J 2G3. Fax: +1 418 663 8756.

Received 12 January 2009; received in revised form 3 February 2009; accepted 4 February 2009. published online 13 February 2009.

Abstract

Various entities and genetic etiologies, including inherited long QT syndrome type 3 (LQT3), contribute to sudden infant death syndrome (SIDS). The goal of our research was to biophysically characterize a new SCN5A mutation (S1333Y) in a SIDS infant. S1333Y channels showed the gain of Na⁺ channel function characteristic of LQT3, including a persistent inward Na⁺ current and an enhanced window current that was generated by a −8mV shift in activation and a +7mV shift in inactivation. The correlation between the biophysical data and arrhythmia susceptibility suggested that the SIDS was secondary to the LQT3-associated S1333Y mutation.