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J Cardiovasc Electrophysiol
2010 Dec 01;2112:1365-72. doi: 10.1111/j.1540-8167.2010.01844.x.
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A novel mutation in the HCN4 gene causes symptomatic sinus bradycardia in Moroccan Jews.
Laish-Farkash A, Glikson M, Brass D, Marek-Yagel D, Pras E, Dascal N, Antzelevitch C, Nof E, Reznik H, Eldar M, Luria D.
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to conduct a clinical, genetic, and functional analysis of 3 unrelated families with familial sinus bradycardia (FSB). mutations in the hyperpolarization-activated nucleotide-gated channel (HCN4) are known to be associated with FSB. three males of Moroccan Jewish descent were hospitalized: 1 survived an out-of-hospital cardiac arrest and 2 presented with weakness and presyncopal events. All 3 had significant sinus bradycardia, also found in other first-degree relatives, with a segregation suggesting autosomal-dominant inheritance. All had normal response to exercise and normal heart structure. Sequencing of the HCN4 gene in all patients revealed a C to T transition at nucleotide position 1,454, which resulted in an alanine to valine change (A485V) in the ion channel pore found in most of their bradycardiac relatives, but not in 150 controls. Functional expression of the mutated ion channel in Xenopus oocytes and in human embryonic kidney 293 cells revealed profoundly reduced function and synthesis of the mutant channel compared to wild-type. we describe a new mutation in the HCN4 gene causing symptomatic FSB in 3 unrelated individuals of similar ethnic background that may indicate unexplained FSB in this ethnic group. This profound functional defect is consistent with the symptomatic phenotype.
Albin,
Sinus node dysfunction in pediatric and young adult patients: treatment by implantation of a permanent pacemaker in 39 cases.
1985, Pubmed
Albin,
Sinus node dysfunction in pediatric and young adult patients: treatment by implantation of a permanent pacemaker in 39 cases.
1985,
Pubmed Azene,
Molecular basis of the effect of potassium on heterologously expressed pacemaker (HCN) channels.
2003,
Pubmed
,
Xenbase Baruscotti,
Physiology and pharmacology of the cardiac pacemaker ("funny") current.
2005,
Pubmed Beder,
Symptomatic sick sinus syndrome in children and adolescents as the only manifestation of cardiac abnormality or associated with unoperated congenital heart disease.
1983,
Pubmed Biel,
Cardiac HCN channels: structure, function, and modulation.
2002,
Pubmed DiFrancesco,
Pacemaker mechanisms in cardiac tissue.
1993,
Pubmed DiFrancesco,
Direct activation of cardiac pacemaker channels by intracellular cyclic AMP.
1991,
Pubmed Gulotta,
Familial occurrence of sinus bradycardia, short PR interval, intraventricular conduction defects, recurrent supraventricular tachycardia, and cardiomegaly.
1977,
Pubmed Herrmann,
HCN4 provides a 'depolarization reserve' and is not required for heart rate acceleration in mice.
2007,
Pubmed Ishii,
Molecular characterization of the hyperpolarization-activated cation channel in rabbit heart sinoatrial node.
1999,
Pubmed Kaupp,
Molecular diversity of pacemaker ion channels.
2001,
Pubmed Lim,
A G protein-gated K channel is activated via beta 2-adrenergic receptors and G beta gamma subunits in Xenopus oocytes.
1995,
Pubmed
,
Xenbase Liu,
Organisation of the mouse sinoatrial node: structure and expression of HCN channels.
2007,
Pubmed Lorber,
Autosomal dominant inheritance of sinus node disease.
1987,
Pubmed Ludwig,
Two pacemaker channels from human heart with profoundly different activation kinetics.
1999,
Pubmed Ludwig,
A family of hyperpolarization-activated mammalian cation channels.
1998,
Pubmed Macri,
Separable gating mechanisms in a Mammalian pacemaker channel.
2002,
Pubmed Mehta,
Familial symptomatic sinus bradycardia: autosomal dominant inheritance.
1995,
Pubmed Milanesi,
Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel.
2006,
Pubmed Moosmang,
Cellular expression and functional characterization of four hyperpolarization-activated pacemaker channels in cardiac and neuronal tissues.
2001,
Pubmed Napolitano,
The slow pace of the heart and the objectives of molecular cardiology.
2010,
Pubmed Nof,
Point mutation in the HCN4 cardiac ion channel pore affecting synthesis, trafficking, and functional expression is associated with familial asymptomatic sinus bradycardia.
2007,
Pubmed
,
Xenbase Robinson,
Hyperpolarization-activated cation currents: from molecules to physiological function.
2003,
Pubmed Schulze-Bahr,
Pacemaker channel dysfunction in a patient with sinus node disease.
2003,
Pubmed Shi,
Distribution and prevalence of hyperpolarization-activated cation channel (HCN) mRNA expression in cardiac tissues.
1999,
Pubmed Stieber,
The hyperpolarization-activated channel HCN4 is required for the generation of pacemaker action potentials in the embryonic heart.
2003,
Pubmed Ueda,
Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia.
2004,
Pubmed Yamada,
G protein regulation of potassium ion channels.
1998,
Pubmed Zha,
Activity-dependent heteromerization of the hyperpolarization-activated, cyclic-nucleotide gated (HCN) channels: role of N-linked glycosylation.
2008,
Pubmed
