Dutch Teams Identify New Intellectual Disability Genes in a Diagnostic Exome Sequencing Plot

There is a new study throughout the New England Journal of Medicine that is underscoring the importance of the mutations in those non-sydromic intellectual disabilities, while also highlighting the potential for using the exome sequencing to diagnose many severe intellectual disability cases that cannot be explained through other genetic tests performed. As part of the pilot program at the Radboud University Nijmegen Medical Center in the Netherlands, researchers went on to turn to exome sequencing in an attempt to diagnose the genetic roots of many intellectual disabilities found in 100 children with severe, non-syndromic forms. Through this sequencing that is done on each of the children and their parents, followed by an extensive analysis and validation testing, they were then able to report casual mutations in around 16 percent of the cases.

Ten of the cases stemmed from de novo mutations to the intellectual disability related genes that were identified in the past and three of the cases involved an X linked mutation that was affecting the known intellectual genes. Another three of the cases were tied in casually with the de novo mutations to new risk genes known as: DYNC1H1, GATAD2B, and CTNNB1. “If we now go back and re-evaluate the patients in a few months time we may actually find a higher diagnostic yield,” co-senior author Joris Veltman, a human genetics researcher at Radboud University Nijmegen Medical Center, told GenomeWeb Daily News. “That’s something that we expected from the start: you will have to go back to the data sometimes for those patients [for which] you’ve not found a diagnostic causal mutation,” he said. “It’s very important to continue with this and look at the data again.”

Although there is a possibility for intellectual disability or mental retardation to come up as a consequence of an infection to settle in, oxygen deprivation, or other non-genetic factors, the study authors went on to explain that most of the cases occur in developed countries that are believed to have genetic causes.