Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiac arrhythmias cause more than 300,000 sudden deaths each year in the USA alone. Long QT syndrome (LQT) is a cardiac disorder that causes sudden death from ventricular tachyarrhythmias, specifically torsade de pointes. Four LQT genes have been identified: KVLQT1 (LQT1) on chromosome 11p15.5, HERG (LQT2) on chromosome 7q35-36, SCN5A (LQT3) on chromosome 3p21-24, and MinK (LQT5) on chromosome 21q22. SCN5A encodes the cardiac sodium channel, and LQT-causing mutations in SCN5A lead to the generation of a late phase of inactivation-resistant whole-cell inward currents. Mexiletine, a sodium channel blocker, is effective in shortening the QT interval corrected for heart rate (QTc) of patients with SCN5A mutations. HERG encodes the cardiac I(Kr) potassium channel. Mutations in HERG act by a dominant-negative mechanism or by a loss-of-function mechanism. Raising the serum potassium concentration can increase outward HERG potassium current and is effective in shortening the QTc of patients with HERG mutations. KVLQT1 is a cardiac potassium channel protein that interacts with another small potassium channel MinK to form the cardiac I(Ks) potassium channel. Like HERG mutations, mutations in KVLQT1 and MinK can act by a dominant-negative mechanism or a loss-of-function mechanism. An effective treatment for LQT patients with KVLQT1 or MinK mutations is expected to be developed based on the functional characterization of the I(Ks) potassium channel. Genetic testing is now available for some patients with LQT.
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PMID:Genetics, molecular mechanisms and management of long QT syndrome. 955 90

The long QT syndrome (LQT) is an inherited cardiac disorder that can cause sudden cardiac death among apparently healthy young individuals due to malignant ventricular arrhythmias. LQT was found to be caused by mutations in four genes LTQ1, LQT2, LQT3 and LQT5, and linkage was reported for an additional locus, LQT4, on chromosome 4q25-27. We have studied a large (n=131) LQT-affected Jewish kindred and identified tight linkage between the LQT-affected status and LQT3 (lod score 6.13, with an estimated recombination fraction of zero). We identified a new point-mutation, A to G substitution at nucleotide 5519 of the SCN5A gene, changing the aspartate 1840 to glycine, D1840G. This is a non-conservative change of an amino acid completely conserved in sodium channels from Molusca to human. The mutation was identified in all affected individuals (n=23), and not identified in all the unaffected family members (n=40), and not in 200 chromosomes of healthy control individuals. The mutation was identified in 3/12 individuals with equivocal phenotype, thus, providing an accurate dignostic tool for all family members. This mutation is currently being used in a cellular electrophysiological model, to characterize the function of the mutated sodium channel in this syndrome.
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PMID:Identification of a new SCN5A mutation, D1840G, associated with the long QT syndrome. Mutations in brief no. 153. Online. 1062 39