PubMed 21070882

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Automatically associated channels: KCNQ1 , Kv11.1 , Kv7.1 , Nav1.5

Title: Prospective, population-based long QT molecular autopsy study of postmortem negative sudden death in 1 to 40 year olds.

Authors: Jonathan R Skinner, Jackie Crawford, Warren Smith, Andrew Aitken, David Heaven, Cary-Anne Evans, Ian Hayes, Katherine R Neas, Simon Stables, Timothy Koelmeyer, Lloyd Denmark, Jane Vuletic, Fraser Maxwell, Kate White, Tao Yang, Dan M Roden, Trond P Leren, Andrew Shelling, Donald R Love,

Journal, date & volume: Heart Rhythm, 2011 Mar , 8, 412-9

PubMed link:

Retrospective investigation of sudden unexplained death in the young (SUDY) reveals that a high proportion is due to inherited heart disease.The purpose of this study was to ascertain the diagnostic value of postmortem long QT (LQT) genetic analysis in a prospective study of SUDY victims 1-40 years old.Denaturing high-performance liquid chromatography or direct sequencing of LQT genes 1, 2, 3, 5, and 6 was performed, in a National New Zealand protocol, in SUDY victims aged 1-40 years.Over 26 months (2006-2008), DNA was stored at autopsy from 52 victims of sudden unexpected death. Further testing revealed a diagnosis in 19 cases (poisoning 4, dilated cardiomyopathy 3, myocarditis 3, other 9). The remaining 33 cases underwent genetic testing (age at death 18 months-40 years, median 25 years). Eighteen (55%) died during sleep or at rest, and 7 (21%) died during light activity. Rare missense variants in LQT genes were found in 5 (15%) cases (confidence interval 3%-27%): T96R in KCNQ1 (11-year-old male), P968L in KCNH2 (32-year-old female), P2006A in SCN5A (34-year-old female), and R67H and R98W in KCNE1 (17- and 38-year-old females, respectively). Evidence of pathogenicity was provided by in vitro evidence (T96R), family phenotype-genotype co-segregation (R98W, P2006A), and/or previous reports (R67H, P968L, P2006A, R98W). Family cardiac investigation was possible in 23 (70%) families and revealed probable cause of death for 5 (15%) other victims (confidence interval 3%-27%).Most community SUDY occurs at rest or during light activity. A diagnostic rate of 15% supports the transition of LQT genetic autopsy, combined with family investigation, into routine medical practice.