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Am J Hum Genet. 2003 Apr;72(4):785-803. Epub 2003 Mar 7.

Unraveling monogenic channelopathies and their implications for complex polygenic disease.

Author information

1
Department Physiology and Biophysics and Division of Human Genetics, Department of Pediatrics, University of California, Irvine, CA 92697, USA. jjgargus@uci.edu

Abstract

Ion channels are a large family of >400 related proteins representing >1% of our genetic endowment; however, ion-channel diseases reflect a relatively new category of inborn error. They were first recognized in 1989, with the discovery of cystic fibrosis transmembrane conductance regulator, and rapidly advanced as positional and functional studies converged in the dissection of components of the action potential of excitable tissues. Although it remains true that diseases of excitable tissue still most clearly illustrate this family of disease, ion-channel disorders now cover the gamut of medical disciplines, causing significant pathology in virtually every organ system, producing a surprising range of often unanticipated symptoms, and providing valuable targets for pharmacological intervention. Many of the features shared among the monogenic ion-channel diseases provide a general framework for formulating a foundation for considering their intrinsically promising role in polygenic disease. Since an increasingly important approach to the identification of genes underlying polygenic disease is to identify "functional candidates" within a critical region and to test their disease association, it becomes increasingly important to appreciate how these ion-channel mechanisms can be implicated in pathophysiology.

PMID:
12629596
PMCID:
PMC1180344
DOI:
10.1086/374317
[Indexed for MEDLINE]
Free PMC Article

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