Today, scientists at the Stanford School of Medicine are on a quest to find out, searching samples of [the] tissue [of a 9-year-old engineering student who dies suddenly] for genetic clues that might explain why the young man's heart suddenly stopped. The "molecular autopsy" is believed the first time that whole-genome sequencing has been used to seek a cause of death, although the Stanford team has used more focused genetic scans to investigate 17 other sudden unexplained deaths. [A medical research team is] scanning [the patient's] DNA for errors that might cause irregular beating of the heart, invisible during traditional dissection....The team's data is still under analysis, and their conclusions won't be published until later this year. But they say they are zeroing in on a set of suspect gene mutations linked to one particular type of rare and poorly understood cause of sudden cardiac death, caused by faulty electrical signaling in a beating heart. If confirmed, the genomes of surviving family members could be searched for similar flaws, and their health monitored closely....Stanford is not the only research facility searching, post-mortem, for killer genes. In Canada, a molecular autopsy of a 21-year-old college student found a genetic mutation that causes a heart problem called Long QT Syndrome. When tested, her mother was found to have the same mutation. At the Mayo Clinic in Minnesota, Dr. Michael Ackerman has performed molecular autopsies of 49 young people who died suddenly. In seven cases, he found suspect mutations in a gene called RyR2 , which regulates the influx of calcium into heart cells.
At least at the present time, the molecular autopsy can be defined as whole-genome sequencing performed post-mortem for patients who have died suddenly of unknown causes. Such testing is initiated because the death is presumed to have been on the basis of a genetic abnormality. Of course, whole-genome sequencing can also be performed ante-mortem so I have introduced the word "suddenly" into this definition. Memes have a way of changing their meaning as they gain currency so my definition may not be valid for long.
The primary goal of an autopsy is to determine the cause of death. Generally speaking, laboratory tests using tissue or serum specimens collected post-mortem are not usually relied upon or even interpretable.This is because many lab values can change rapidly post-mortem. Such problems can be partly ameliorated if samples are collected and preserved rapidly after death. A major exception can be bacterial and viral cultures in the case of suspected infectious disease as the cause of death or toxicology studies in forensic cases.
I have posted previous notes about the need for greater integration of clinical pathology with surgical pathology (see: Integration of Anatomic and Clinical Pathology ). This has been the norm in the field of hematopathology for two or more decades in which reports are integrated and serve to correlate a patient's hematologic lab tests with both immunohistochemistry (IHC) results and morphologic findings (see: Reinventing Pathology: The Hematopathologist as a Model for the Pathologist of the Future ). In the case of molecular autopsies, we have a new instance of genomic testing evolving as a key component of autopsy pathology.
I have been collecting memes that have been cropping up to describe the use of clinical lab science and technology in new ways to diagnose disease. The last example of what I will call a "pathology meme" was the liquid biopsy (see: Does the New Term "Liquid Biopsy" Make Any Sense? ; Rapid Adoption of the Term "Liquid Biopsy" on the Web ; Continuing Discussion about the "Liquid Biopsy" ). Another such pathology meme has now surfaced -- the molecular autopsy (see: Stanford's 'molecular autopsies' hope to help grieving families ). A Google search for "molecular autopsy" produced nearly 8,000 hits . Below is an excerpt from a recent article using the term
Today, scientists at the Stanford School of Medicine are on a quest to find out, searching samples of [the] tissue [of a 9-year-old engineering student who dies suddenly] for genetic clues that might explain why the young man's heart suddenly stopped. The "molecular autopsy" is believed the first time that whole-genome sequencing has been used to seek a cause of death, although the Stanford team has used more focused genetic scans to investigate 17 other sudden unexplained deaths. [A medical research team is] scanning [the patient's] DNA for errors that might cause irregular beating of the heart, invisible during traditional dissection....The team's data is still under analysis, and their conclusions won't be published until later this year. But they say they are zeroing in on a set of suspect gene mutations linked to one particular type of rare and poorly understood cause of sudden cardiac death, caused by faulty electrical signaling in a beating heart. If confirmed, the genomes of surviving family members could be searched for similar flaws, and their health monitored closely....Stanford is not the only research facility searching, post-mortem, for killer genes. In Canada, a molecular autopsy of a 21-year-old college student found a genetic mutation that causes a heart problem called Long QT Syndrome. When tested, her mother was found to have the same mutation. At the Mayo Clinic in Minnesota, Dr. Michael Ackerman has performed molecular autopsies of 49 young people who died suddenly. In seven cases, he found suspect mutations in a gene called RyR2 , which regulates the influx of calcium into heart cells.At least at the present time, the molecular autopsy can be defined as whole-genome sequencing performed post-mortem for patients who have died suddenly of unknown causes. Such testing is initiated because the death is presumed to have been on the basis of a genetic abnormality. Of course, whole-genome sequencing can also be performed ante-mortem so I have introduced the word "suddenly" into this definition. Memes have a way of changing their meaning as they gain currency so my definition may not be valid for long.
The primary goal of an autopsy is to determine the cause of death. Generally speaking, laboratory tests using tissue or serum specimens collected post-mortem are not usually relied upon or even interpretable.This is because many lab values can change rapidly post-mortem. Such problems can be partly ameliorated if samples are collected and preserved rapidly after death. A major exception can be bacterial and viral cultures in the case of suspected infectious disease as the cause of death or toxicology studies in forensic cases.
I have posted previous notes about the need for greater integration of clinical pathology with surgical pathology (see: Integration of Anatomic and Clinical Pathology ). This has been the norm in the field of hematopathology for two or more decades in which reports are integrated and serve to correlate a patient's hematologic lab tests with both immunohistochemistry (IHC) results and morphologic findings (see: Reinventing Pathology: The Hematopathologist as a Model for the Pathologist of the Future ). In the case of molecular autopsies, we have a new instance of genomic testing evolving as a key component of autopsy pathology.