According to a study published online in Nature Genetics, researchers have identified three new mutations associated with megalencephaly (enlarged brain size), cancer, autism, hydrocephalus, skin growth disorders, epilepsy, and vascular anomalies.

The study, led by Seattle Children’s Research Institute, provides further evidence that the genetic make-up of an individual is not entirely determined at the time of conception. Earlier studies have shown that genetic changes can also occur after conception. In addition, the teams finding may lead to the possibilities of new treatments for these diseases.

The researchers discovered mutations in three genes, AKT3, PIK3R2 and PIK3CA, all of which are present in humans. However, variations in these genes lead to a wide variety of disorders, including cancer, megalencephaly, and other disorders.

Previous studies have found an associated between the PIK3CA gene and cancer, and it appears that this gene is able to make cancer more aggressive.

James Olson, M.D., Ph.D., a pediatric cancer expert at Seattle Children’s and Fred Hutchinson Cancer Research Center who was not affiliated with the study, explained:

“This study represents ideal integration of clinical medicine and cutting-edge genomics. I hope and believe that the research will establish a foundation for successfully using drugs that were originally developed to treat cancer in a way that helps normalize intellectual and physical development of affected children.”

The team ‘knocked it out of the park’ by deep sequencing exceptionally rare familial cases and unrelated cases to identify the culprit pathway.”

AKT3, PIK3R2 and PIK3CA all encode core components of the phosphatidylinositol-3-kinase (P13K)/AKT pathway, the “culprit pathway” referenced by Olson.

The teams findings provide new insight into chronic childhood conditions and disease and could lead to new treatments within ten years.

William Dobyns, M.D., a geneticist at Seattle Children’s Research Institute, explained:

“This is a huge finding that provides not only new insight for certain brain malformations, but also, and more importantly, provides clues for what to look for in less severe cases and in conditions that affect many children.

Kids with cancer, for example, do not have a brain malformation, but they may have subtle growth features that haven’t yet been identified. Physicians and researchers can now take an additional look at these genes in the search for underlying causes and answers.”

The next step for the researchers is to investigate deeper into their findings and uncover even more about the potential medical implications for children.

Jean-Baptiste Rivière, PhD, at Seattle Children’s Research Institute, concluded:

“Based on what we’ve found, we believe that we can eventually reduce the burden of and need for surgery for kids with hydrocephalus and change the way we treat other conditions, including cancer, autism, and epilepsy. This research truly helps advance the concept of personalized medicine.”

Written by Grace Rattue