This report describes a study aimed at validating and implementing a cost-effective molecular autopsy at the Harris County Institute of Forensic Sciences in Houston, Texas, to investigate sudden unexplained deaths of infants and young people; the document provides a strategy for implementation, through molecular autopsies, in medicolegal investigations of sudden death cases.
This research project described in this document examined autopsy reports of young adults younger than 40 years, children, and infants less than one year old, from 2004 to 2012, in Houston, Texas. Cases classified as undetermined, sudden infant death syndrome (SIDS), or undetermined/co-sleeping, were culled for further analysis, and a cohort of 429 decedents was selected for postmortem genetic screening. The report presents the research methodology and analysis, starting with the researchers’ isolation of genomic DNA from the cohort from extracted blood spots, previously dried on Whatman FTA® bloodstain cards. Of the 429 individuals initially selected for testing, 351 DNA samples were of sufficient quality and quantity for sequencing. Thirteen of the decedents were found to have reportable pathogenic genetic variants, representing 3.7 percent of the total cohort that was successfully sequenced. The genetic-screening strategy presented in this report highlights a new transition between research and specific clinical cases to implementation of the molecular autopsy as a cost-effective standard of care in postmortem examinations. The researchers kept the cost below $600 per sample by targeting selected exons. An unexpected finding of this study was the low percentage of individuals found to have a pathogenic variation compared to previous reports, despite consistent cohort demographics. This report also notes that the study included the largest heterogeneous cohort of sudden death (SD) cases evaluated by a large, targeted sequencing panel for genes associated with SIDS and Sudden Unexplained Death (SUD).