The order of diagnosing rare diseases is being upended by exome sequencing, Alyson MacInnes from the Sanger Research and Landsteiner Laboratory in Amsterdam tells the Journal of the American Medical Association.
JAMA in particular focuses on the story of a Dutch boy who developed learning disabilities, hypotonia, and more, but for whom tests for certain neurological diseases and chromosomal abnormalities came up empty. But after the boy's father pursued exome sequencing, a de novo mutation was identified in a ribosomal protein gene, though it only appeared to explain some of the boy's symptoms. The father then contacted the researchers who've studied the gene to learn more.
"Instead of a patient going to the clinic with a list of features, getting a diagnosis, doing the exome sequencing, and then enlisting a researcher to figure out the molecular mechanism, it's going in reverse. Now the patient, armed with exome data, contacts the researcher, who figures out the mechanism, and then with the clinician is able to determine the diagnosis," MacInnes says.
But, as Ricki Lewis writes in JAMA, exome sequencing only leads to diagnoses in about a quarter to a third of cases, and even less often to treatments. Still, she notes that as the human genome becomes better annotated, the hit rate will increase, and exome sequencing will move into predictive medicine.