Changes in the exome (the coding part of the genome) could help diagnose unexplained intellectual disabilities, according to two studies from Radboud University Nijmegen Medical Centre in the Netherlands that were presented at the American Society of Human Genetics 2012 meeting in San Francisco. Exome sequencing just focuses on the 21,000 protein-coding genes that make up 1% to 2% of the human genome.
The cause of intellectual disability is unknown in around half of patients, and there are no other cases in most of these families. Being able to make early diagnoses improves support for children and their parents, including early educational intervention, help for behavioral problems, and screening for any associated health issues, allowing children to reach their full potential, said researcher Marjolein Willemsen. Knowing the genetic background of the impairments can also enable genetic counseling.
However, diagnosis can be difficult because a wide range of features characterizes these disorders, and the underlying genetic causes can vary widely, researcher Tjitske Kleefstra said. "As a result, many parents go from one doctor to another in search of a diagnosis and treatment for their child," she added.
In the first study, the researchers sequenced the exomes in 100 patients and their parents and found 79 genes with mutations that were in the children and not the parents. The team described 16 of these mutations as "causative," and three were in new genes.
In a second study at the same center, after genome-wide analyses of 253 people with intellectual disabilities, 47 patients remained undiagnosed and their exomes were sequenced. The researchers correlated biological and behavioral features of each individual with their DNA, and found the likely genetic causes of unexplained forms of intellectual disability in 36%.
These are small studies, and more studies in larger groups are needed, but they suggest that exome sequencing could be used as a diagnostic tool in patients with intellectual disability of unknown cause.