Postmortem genetic testing identified LQTS-associated mutations in 20% of young cases with autopsy-negative sudden unexplained death, with a significantly higher prevalence in women (44% vs 6.7%, p<0.008).
Observational (n=49)
Does comprehensive postmortem LQTS genetic testing identify pathogenic mutations in young patients with autopsy-negative sudden unexplained death?
Postmortem genetic testing for LQTS identifies a putative cardiac channel mutation in 20% of autopsy-negative sudden unexplained deaths in the young, supporting its use in molecular autopsies.
OBJECTIVES: This study sought to determine the spectrum and prevalence of long QT syndrome (LQTS)-associated mutations in a large cohort of autopsy-negative sudden unexplained death (SUD). BACKGROUND: Potentially heritable arrhythmia syndromes may explain a significant proportion of SUD in the young. Here, comprehensive postmortem LQTS genetic testing was performed in a cohort of SUD cases. METHODS: From September 1998 to March 2004, 49 cases of SUD (30 male patients, average age at death 14.2 +/- 10.9 years) were referred by medical examiners/coroners to Mayo Clinic's Sudden Death Genomics Laboratory. Using polymerase chain reaction, denaturing high-performance liquid chromatography, and direct DNA sequencing, open reading frame/splice site mutational analysis was conducted for all 8 genes implicated in the pathogenesis of either LQTS (LQT1 to LQT6) or multisystem disorders involving either QT or QU prolongation. RESULTS: Ten LQTS-associated mutations (4 novel) were discovered in 10 SUD cases (20%, 8 female patients, average age at death 18.0 +/- 11.8 years). The LQTS susceptibility mutations LQT1 (5), LQT2 (3), and LQT3 (2) were far more common among women (8 of 18, 44%) than men (2 of 30, 6.7%, p < 0.008). The activities at the time of SUD included sleep (5), exertion (2), auditory arousal (1), and undetermined (2). Sudden death was the sentinel event in two-thirds of the cases. CONCLUSIONS: In this cardiac channel-focused molecular autopsy investigation of SUD, over one-third of decedents harbored a putative cardiac channel mutation: 7 previously reported to host mutations in the RyR2-encoded calcium release channel and now 10 with LQTS susceptibility mutations. Accordingly, postmortem cardiac channel genetic testing should be pursued in the evaluation of autopsy-negative SUD.
Tester et al. (Sat,) conducted a observational in Sudden unexplained death (SUD) (n=49). LQTS-associated mutations was evaluated on Presence of LQTS-associated mutations. Postmortem genetic testing identified LQTS-associated mutations in 20% of young cases with autopsy-negative sudden unexplained death, with a significantly higher prevalence in women (44% vs 6.7%, p<0.008).
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