Gene Mutation in Children

At the age of three a young boy with mild developmental delays and physical characteristics with a large body and large head circumference came to Duke University School of Medicine to be diagnosed. A genetic analysis showed mutation of a specific gene, known as ASCL2 which had never been singled out as causing disease.

The child’s doctor Vandana Shashi, Professor of Pediatrics for the Division of Medical Genetics at Duke University School of Medicine http://pediatrics.duke.edu/divisions/medical-genetics   told the parents their son likely had a rare and yet unidentified disease.

Shashi wanted to solve the mystery case so she contacted the Undiagnosed Diseases Network (UDN) www.genome.gov at NIH. This Network links Duke and six other medical teaching sites around the country where the participating centers pool information and innovations on rare diseases that are stumping the broader medical community.

Within just six weeks the boy’s doctor connected to other UDN research labs and to an international database of genes and disease characteristics called GeneMatcher. Dr. Shashi was able to find that five other children had all the same physical features and the ASXL2 gene mutation.

The new disease which still has no name does have similarities to two other rare genetic disorders arising from related genes. For example one genetic disorder called Bohring-Opitz syndrome is the result of a mutation of the ASXL1 gene while the other genetic disorder called Bainbridge-Ropers syndrome is caused by a flaw in the ASXL3 gene. Both conditions are rare and can result in similar, but more severe impairments.

It is still unknown how the ASXL2 genetic mutation arises, but Dr. Shashi said. “Identifying the root cause of a medical condition is a first step, and could help to drive new therapies and treatment approaches.