Clinical InvestigationGeneticsAssociation of torsades de pointes with novel and known single nucleotide polymorphisms in long QT syndrome genes
Section snippets
Methods
Genomic DNA was obtained from a small subset of patients enrolled in the DIAMOND studies.17 These studies focused on the effects of dofetilide on 2 populations of patients: 1 with congestive heart failure (CHF) and another with recent myocardial infarction (MI) associated with left ventricular dysfunction. DNA samples were obtained with appropriate informed consent from the patients, and the requests were reviewed by the institutional review boards. Retrospective consent and sample collection
Results
The large number of individuals and the extensive range of sequences analyzed led us to screen for mutations with Transgenomic WAVE denaturing high-performance liquid chromatography. Complete data were obtained from all 34 patients with TdP for 109 of the 112 exons in the 7 genes studied. Exons 1, 11, and 13 in KCNH2 were not amenable to this screening procedure because of their high guanine-cytosine content. Instead, these exons were directly sequenced in 28 patients. DNA from the other 6
Discussion
Although QT prolongation has long been known to be a risk factor for sudden cardiac death, its importance in the general population and how genetic predisposition may affect sudden death have been controversial. Much of this controversy may arise from differences in the populations examined.27 QT is affected by age, sex, BMI, hypertension, diabetes, and other risk factors; therefore, genetic and environmental contributions to both QT and sudden death can vary significantly among different
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Explaining sudden infant death with cardiac arrhythmias: Complete exon sequencing of nine cardiac arrhythmia genes in Dutch SIDS cases highlights new and known DNA variants
2020, Forensic Science International: GeneticsCitation Excerpt :Furthermore they were all classified as (likely) benign. Both ANK2 c.9854 t > c and c.9900c > a were first encountered by Mank-Seymour et al. [33], who found both of them in low frequencies in TdP patients and controls, as well as the rare DNA variants ANK2 c.7106 t > c, and ANK2 c.8503c > t. The frequencies of these DNA variants in the Dutch SIDS cases (0.09 and 0.02, resp.)
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2010, Heart RhythmCitation Excerpt :Recently, two studies examining the role of ion channel genetic variants in either the development of life-threatening torsades de pointes dysrhythmia or their association with sudden cardiac death identified A572D in their cohorts. In a study by Mank-Seymour et al,19 A572D seemed overrepresented in proarrhythmic cases, being identified in approximately 3% (1/34) of European torsades de pointes–positive congestive heart failure or myocardial infarction cases compared with approximately 0.7% (4/555) of European controls. Similarly, Albert et al12 identified A572D in 1.6% (1/60) of female sudden cardiac death victims compared with 0.27% (2/733) of controls.
Rare Variation in Drug Metabolism and Long QT Genes and the Genetic Susceptibility to Acquired Long QT Syndrome
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