DUGi

Comparative diagnostic yield of targeted NGS panels versus whole-exome sequencing in post-mortem evaluation of sudden cardiac death

http://dugi.udg.edu/item/http:@@@@hdl.handle.net@@10256@@28496

BACKGROUND: Life loss due to sudden cardiac death among young adults has a significant impact on the families and the larger community. As opposed to coronary artery disease being the most common cause of sudden cardiac death in the elderly, young people less than 35 years old are often suspected to die from an inherited cardiac condition. Unfortunately, a substantial proportion of juvenile sudden cardiac death cases remain unexplained; therefore, making comprehensive investigations essential to find the elusive causes of death and hopefully enable cascade family screenings. Currently, molecular autopsy represents an effective diagnostic tool and one of the many pillars in the multidisciplinary approach to sudden cardiac death diagnosis. Within next-generation sequencing technologies, there are two main approaches currently used: targeted gene panels and whole-exome sequencing, but their comparative performance and diagnostic yield across the different sudden cardiac death phenotypes have not been consistently characterized yet. OBJECTIVE: To compare diagnostic yield and interpretability of targeted next-generation sequencing panels versus whole-exome sequencing across sudden cardiac death in individuals under 50 years of age. STUDY DESIGN AND SETTING: This is a prospective, single-gate diagnostic yield study carried out over a 12-18 month period across Catalonia (Spain). The study will involve collaboration of Institut de Medicina Legal i Ciències Forenses de Catalunya (IMLCFC) in Barcelona, Spain, in a coordinated referral network including central sequencing in the Cardiovascular Genetics Center at the Research Biomedical Institute of Girona (IDIBGI). PARTICIPANTS: Consecutive individuals under 50 years for whom sudden cardiac death was established by forensic investigation, and suspected to have inherited cardiac disease, will be enrolled from participating centers

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