Hoping to better target patient treatment, the investigators went about tracking down the exact cause of adrenal insufficiency. They proceeded to analyze part of the genome that codes for genes in one patient's DNA (whole-genome sequencing being still too expensive for the time being). To their great surprise, the analysis indicated the presence of two mutations in POMC, the gene that codes for ACTH, in the patient. Direct sequencing of the POMC gene in DNA from the second patient confirmed the occurrence of one of the mutations in that child as well. The researchers then collaborated with Dr. Michel Bouvier (University of Montreal) and Dr. Nicole Gallo-Payet (University of Sherbrooke) to validate the discovery by performing in vitro tests on cells using two synthetic ACTHs produced for the experiment: one normal and the other carrying the mutation observed in both children. These studies showed that, while high levels were detected in the blood, the mutant ACTH was inactive. Due to technical limitations, the standard diagnostic test that detects ACTH was unable to distinguish between the normal and the mutated form found in the patients.
"The genome analysis allowed us to incriminate the POMC gene. Since the gene was not suspect according to the blood tests, we would have missed the cause of the disease without this new technique," concludes Dr. Deladoy, a physician and researcher in endocrinology and diabetology.
This case of personalized medicine made possible through novel genomic techniques is just the tip of the iceberg. In the near future, investigators hope to succeed in refining the treatment of many patients using these techniques.
|Contact: William Raillant-Clark|
University of Montreal