Sick sinus syndrome with HCN4 mutations shows early onset and frequent association with atrial fibrillation and left ventricular noncompaction

Jensen, 2014, Incidence of and risk factors for sick sinus syndrome in the general population, J Am Coll Cardiol, 64, 531, 10.1016/j.jacc.2014.03.056 Ishikawa, 2016, Inherited bradyarrhythmia: a diverse genetic background, J Arrhythm, 32, 352, 10.1016/j.joa.2015.09.009 Benson, 2003, Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A), J Clin Invest, 112, 1019, 10.1172/JCI200318062 Verkerk, 2015, Pacemaker activity of the human sinoatrial node: an update on the effects of mutations in HCN4 on the hyperpolarization-activated current, Int J Mol Sci, 16, 3071, 10.3390/ijms16023071 Abe, 2014, Sodium channelopathy underlying familial sick sinus syndrome with early onset and predominantly male characteristics, Circ Arrhythm Electrophysiol, 7, 511, 10.1161/CIRCEP.113.001340 Chandler, 2009, Molecular architecture of the human sinus node: insights into the function of the cardiac pacemaker, Circulation, 119, 1562, 10.1161/CIRCULATIONAHA.108.804369 Macri, 2014, A novel trafficking-defective HCN4 mutation is associated with early-onset atrial fibrillation, Heart Rhythm, 11, 1055, 10.1016/j.hrthm.2014.03.002 Milano, 2014, HCN4 mutations in multiple families with bradycardia and left ventricular noncompaction cardiomyopathy, J Am Coll Cardiol, 64, 745, 10.1016/j.jacc.2014.05.045 Schweizer, 2014, The symptom complex of familial sinus node dysfunction and myocardial noncompaction is associated with mutations in the HCN4 channel, J Am Coll Cardiol, 64, 757, 10.1016/j.jacc.2014.06.1155 Nof, 2007, Point mutation in the HCN4 cardiac ion channel pore affecting synthesis, trafficking, and functional expression is associated with familial asymptomatic sinus bradycardia, Circulation, 116, 463, 10.1161/CIRCULATIONAHA.107.706887 Zolles, 2006, Pacemaking by HCN channels requires interaction with phosphoinositides, Neuron, 52, 1027, 10.1016/j.neuron.2006.12.005 Duhme, 2013, Altered HCN4 channel C-linker interaction is associated with familial tachycardia-bradycardia syndrome and atrial fibrillation, Eur Heart J, 34, 2768, 10.1093/eurheartj/ehs391 Laish-Farkash, 2010, A novel mutation in the HCN4 gene causes symptomatic sinus bradycardia in Moroccan Jews, J Cardiovasc Electrophysiol, 21, 1365, 10.1111/j.1540-8167.2010.01844.x Milanesi, 2006, Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel, N Engl J Med, 354, 151, 10.1056/NEJMoa052475 Schweizer, 2010, cAMP sensitivity of HCN pacemaker channels determines basal heart rate but is not critical for autonomic rate control, Circ Arrhythm Electrophysiol, 3, 542, 10.1161/CIRCEP.110.949768 Ueda, 2004, Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia, J Biol Chem, 279, 27194, 10.1074/jbc.M311953200 Priori, 2002, Natural history of Brugada syndrome: insights for risk stratification and management, Circulation, 105, 1342, 10.1161/hc1102.105288 Pambrun, 2014, Myotonic dystrophy type 1 mimics and exacerbates Brugada phenotype induced by Nav1.5 sodium channel loss-of-function mutation, Heart Rhythm, 11, 1393, 10.1016/j.hrthm.2014.04.026 Herrmann, 2007, HCN4 provides a ‘depolarization reserve’ and is not required for heart rate acceleration in mice, EMBO J, 26, 4423, 10.1038/sj.emboj.7601868 Lakatta, 2010, A coupled SYSTEM of intracellular Ca2+ clocks and surface membrane voltage clocks controls the timekeeping mechanism of the heart’s pacemaker, Circ Res, 106, 659, 10.1161/CIRCRESAHA.109.206078 McNair, 2004, SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and arrhythmia, Circulation, 110, 2163, 10.1161/01.CIR.0000144458.58660.BB Olson, 2005, Sodium channel mutations and susceptibility to heart failure and atrial fibrillation, JAMA, 293, 447, 10.1001/jama.293.4.447 Liang, 2013, HCN4 dynamically marks the first heart field and conduction system precursors, Circ Res, 113, 399, 10.1161/CIRCRESAHA.113.301588 Spater, 2013, A HCN4+ cardiomyogenic progenitor derived from the first heart field and human pluripotent stem cells, Nat Cell Biol, 15, 1098, 10.1038/ncb2824