Population
Patients suffering from sinus node dysfunction, progressive cardiac conduction disease, and idiopathic…
Design
Preclinical
Key result
The HCN4 D553N mutation caused reduced membranous expression and decreased If currents due to a dominant-negative trafficking defect, linking it to sinus nodal dysfunction and QT prolongation.
Authors
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Suggests HCN4 sequencing in unexplained sinus node dysfunction with QT prolongation; leaves open clinical translation pending human studies.
The loss of function of HCN4 due to the D553N mutation is associated with sinus nodal dysfunction and may underlie clinical features of QT prolongation and polymorphic ventricular tachycardia.
Ueda et al. (2004) studied Sinus node dysfunction, progressive cardiac conduction disease, and idiopathic ventricular fibrillation. HCN4 D553N mutation was evaluated on In vitro functional expression and If currents. The HCN4 D553N mutation caused reduced membranous expression and decreased If currents due to a dominant-negative trafficking defect, linking it to sinus nodal dysfunction and QT prolongation.