@article{113fc1fde44b4be3915729a7fdadc2fc,
title = "Recent genetic discoveries implicating ion channels in human cardiovascular diseases",
abstract = "The term 'channelopathy' refers to human genetic disorders caused by mutations in genes encoding ion channels or their interacting proteins. Recent advances in this field have been enabled by next-generation DNA sequencing strategies such as whole exome sequencing with several intriguing and unexpected discoveries. This review highlights important discoveries implicating ion channels or ion channel modulators in cardiovascular disorders including cardiac arrhythmia susceptibility, cardiac conduction phenotypes, pulmonary and systemic hypertension. These recent discoveries further emphasize the importance of ion channels in the pathophysiology of human disease and as important druggable targets.",
author = "George, {Alfred L.}",
note = "Funding Information: Exome sequencing has been widely applied to examine the prevalence and diversity of rare genetic variants in various populations. The National Heart, Lung and Blood Institute Grand Opportunity funded Exome Sequencing Project (ESP) cataloged variants in 6500 subjects [ 7 ]. Mining of these data has revealed surprisingly high rates of rare variants predicted to have deleterious effects within ion channel encoding genes previously associated with congenital arrhythmia susceptibility [ 8–10 ]. A similar observation was made in the NIH based exome cohort of 870 participants not previously selected for specific cardiac disorders [ 11 ]. In the NIH study, 360 variants were identified in genes, many of which encode ion channels, previously associated with arrhythmia predisposition and four subjects were later revealed to have LQTS. The explanation for these findings could be an underestimation of the population prevalence of these conditions, false positive detection, or mostly likely a combination of these two possibilities. Funding Information: The author is supported by a grant from the National Institutes of Health ( HL083374 ). ",
year = "2014",
month = apr,
doi = "10.1016/j.coph.2013.11.011",
language = "English (US)",
volume = "15",
pages = "47--52",
journal = "Current Opinion in Pharmacology",
issn = "1471-4892",
publisher = "Elsevier BV",
number = "1",
}
