Isabelle Baró

Abstract The long QT syndrome type 3 (LQT3) is a cardiac channelopathy caused by gain-of-function mutations in the SCN5A gene, encoding the sodium channel Nav1.5. As Nav1.5 is expressed in cardiomyocytes but also in cardiac fibroblasts, we investigated whether the LQT3-causing p.ΔQKP1507-1509 (ΔQKP) SCN5A mutation alters cardiac fibroblast phenotype.

Introduction Cardiac myocyte action potentials, generated by the delicate balance of inward (INa, ICa, If) and outward (IKAch, IK1, Ito, IKur, IKr, IKs) currents through the sarcolemma, are critical for coordinating the contractions of the myocardium (Grant, 2009). Disruptions, genetic or acquired, to ion channel function increase the risk of abnormal heart rhythms.

Methods and Results We combined whole‐exome sequencing and linkage analysis to identify the genetic variant likely causing Brugada syndrome in a pedigree for which SCN5A mutations had been excluded. This approach identified 6 genetic variants cosegregating with the Brugada electrocardiographic pattern within the pedigree. In silico gene prioritization pointed to 1 variant residing in KCNAB2, which encodes the voltage‐gated K+ channel β2‐subunit (Kvβ2‐R12Q).