Bringing Autopsies Into the Molecular Genetic Era

Articles, see p 2705 and p 2716 > “To investigate the causes of death, to examine carefully the condition of organs, after such changes have gone on in them as to render existence impossible, and to apply such knowledge to the prevention and treatment of disease is one of the highest objects of the physician.” > > —Sir William Osler1 Imagine the tragedy caused by the sudden and unexpected death of a loved one or family member. Without a premorbid course of worsening health or a previous diagnosis of life-threatening disease, the natural question that plagues surviving family members after sudden cardiac death (SCD) is, “why did this happen?” Autopsies in people age 1 to 40 years with sudden unexpected death identify a clear structural cardiovascular cause in approximately two-thirds of cases, with one-third designated “autopsy-negative sudden unexplained death syndrome” or SUDS.2 Whole exome molecular autopsy has the ability to clarify genetic contributions to SUDS, when properly used.3 And furthermore, postmortem DNA sequencing can also be very valuable for family members when people die with a clear genetic disorder, such as Marfan syndrome, hypertrophic cardiomyopathy, or arrhythmogenic right ventricular cardiomyopathy, which is now more commonly called arrhythmogenic cardiomyopathy (ACM), a term used to encompass cardiomyopathy affecting the right, left, or both ventricles with prominent arrhythmia. Two articles in the current issue of Circulation support this approach, taking on the important challenge of clarifying the genetic contributions to sudden unexplained death.4,5 Finland is somewhat geographically isolated in Northern Europe.6 Gene variation in the Finnish population has been remarkably well studied, in part because of its reduced ethnic diversity and its high level of genetic homogeneity. Junttila and colleagues4 focused on autopsies from 4031 consecutive SCD victims in Northern Finland. Coronary heart disease was the most common …