Send to:

Choose Destination
See comment in PubMed Commons below
J Cardiovasc Electrophysiol. 2010 Dec;21(12):1365-72. doi: 10.1111/j.1540-8167.2010.01844.x.

A novel mutation in the HCN4 gene causes symptomatic sinus bradycardia in Moroccan Jews.

Author information

  • 1Heart Institute, Sheba Medical Center, Tel Hashomer, Israel Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.



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.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley Icon for PubMed Central
    Loading ...
    Write to the Help Desk