Details of the study were first published this month in the New England Journal of Medicine here: A Mosaic Activating Mutation in AKT1 Associated with the Proteus Syndrome.
Proteus Syndrome is an extremely rare condition involving the uncontrolled, typically asymmetric overgrowth of various body tissues, bones and other parts. Identification involves noting the unequal distribution of affected areas, the appearance of the suspected syndrome among only one member in a family, and continued growth over time of the body areas experiencing accelerated growth.
"Proteus syndrome does not run in families, but faulty genes were believed to be responsible. Some experts proposed that the condition might be a genetic mosaicism. Mosaic disorders arise when a genetic mutation occurs spontaneously during embryonic development," the NIH report states.
A research team at the NIH’s National Human Genome Research Institute (NHGRI) used a technique called whole-exome sequencing to examine the cells of six affected individuals in order to determine if their hypothesis was correct. What they discovered was a gene that had already been implicated in cancer studies and related therapies.
"The analysis reveled a single-letter misspelling in the genome of affected cells," The NIA states. "The mutated gene, called AKT1, is a known ocogene—a gene that can promote the uncontrolled cell growth associated with cancer."
Further confirmation of the role played by a gene defect was found by testing 29 others, for who 26 showed the variation. No variations have been found beyond affected individuals.
Accelerated AKT protein activity had been observed in previous research into the cause of the syndrome.
The focus now is on developing a drug to inhibit the increase in AKT protein activity.
For further reading, see: Gene Variant in Proteus Syndrome Identified.