Postmortem long QT syndrome genetic testing for sudden unexplained death in the young

Area of Science:

• Cardiovascular Genetics
• Molecular Autopsy
• Sudden Cardiac Death

Background:

• Sudden unexplained death (SUD) in young individuals may be linked to heritable arrhythmia syndromes.
• Comprehensive postmortem genetic testing for LQTS was conducted in a cohort of SUD cases.

Purpose of the Study:

• To determine the spectrum and prevalence of long QT syndrome (LQTS)-associated mutations in a large cohort of autopsy-negative SUD.
• To investigate the role of cardiac channel mutations in unexplained deaths.

Main Methods:

• Analysis of 49 autopsy-negative SUD cases (September 1998-March 2004).
• Utilized polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing for mutational analysis.
• Screened all 8 genes associated with LQTS (LQT1-LQT6) and related QT prolongation disorders.

Main Results:

• Ten LQTS-associated mutations (4 novel) were found in 10 SUD cases (20%).
• LQTS mutations were significantly more common in females (44%) than males (6.7%).
• Identified mutations in LQT1, LQT2, and LQT3 genes; activities at death included sleep and exertion.

Conclusions:

• Over one-third of SUD decedents harbored a cardiac channel mutation, including LQTS susceptibility mutations.
• Postmortem cardiac channel genetic testing is crucial for evaluating autopsy-negative SUD.
• This study underscores the importance of molecular autopsy in identifying genetic causes of sudden death.