Sudden death in the young (SDY) is a tragic event, with devastating consequences for the family who must endure both the unexpected loss of their child and the possibility of harboring a familial disorder that threatens the health and survival of the remaining members. Due to lack of evidence, there is little consensus within the scientific community regarding the best method for preventing SDY. To address this knowledge gap, the National Heart, Lung, and Blood Institute (NHLBI), National Institute of Neurologic Disorders and Stroke (NINDS) and Centers for Disease Control and Prevention (CDC) created the SDY Registry, with the goal of defining the genomic and mechanistic basis for SDY. The Utah SDY Center (Martin Tristani-Firouzi and Mark Yandell, Principal Investigators) was recently selected as one of three funded centers to uncover the genomic and mechanistic basis for SDY.
Over the next 4 years, we proposed to (Aim 1): Provide the SDY Case Registry with the bioinformatics expertise that will enable the discovery of the genomic basis for autopsy-negative SDY, using whole-exome/genome sequencing; (Aim 2): Characterize novel SDY disease genes, alleles and disease mechanisms, using cell- and model organism-based assays; and (Aim 3): Integrate our clinical expertise in SDY to phenotype, genotype, risk-stratify and counsel surviving family members. The Utah SDY Center’s multi-disciplinary research plan will allow us to discover, validate and characterize new sudden death genes, alleles and mechanisms at a scale and resolution not previously possible and thus establish the foundation for future screening strategies and preventative measures.