London: Scientists have discovered 15 gene mutation that can cause intellectual disabilities, a study has found.
Intellectual disabilities are often caused by a mutation that damages a gene, preventing the associated protein from functioning properly.
However, a mutation can also change the function of a gene. As a result, the gene in question acts in a completely different way.
Researchers from Radboud University Medical Centre in Netherlands discovered this mechanism in fifteen genes playing a role in the development of intellectual disabilities.
Genes are responsible for protein production in cells. A common cause of intellectual disabilities is a de novo mutation (ie a mutation present in a child, but not in its parents) damaging a gene so severely that it is no longer able to produce functional proteins.
The resulting protein defect will cause illness. In a number of disease-related genes, it is shown that a de novo mutation does not eliminate the gene, but probably alters its function. These mutations are only located on specific parts of the gene.
In order to find out how often this mechanism is involved, researchers combined the gene mutations in Dutch patients with a large international database comprising de novo mutations in patients.
"With our method, we were able to detect genes in which mutations not so much eliminate as affect the gene in another way," said Christian Gilissen, who led the research.
"We found fifteen genes in which mutations cluster closely together, twelve of which being associated with developmental disorders," said Gilissen.
"We also found three new genes that are likely to play a role in the development of intellectual disabilities as well," he said.
The de novo mutations that were found only change a very small part of a protein. The function of the protein remains largely, but not entirely the same.
"The mutations are more likely to affect superficial parts of the proteins. These disturb interactions with other proteins and cause problems," said Gilissen.
"Although mutations eliminating genes were often thought to be the main cause of intellectual disabilities, mutations altering the function of genes are now shown to be an important factor as well," he said.
The three newly-discovered genes playing a role in the development of intellectual disabilities provide new diagnostic possibilities for patients.
"It is important that we have discovered a mechanism that has not yet been a focus of study. We expect this mechanism to play a role in a much larger proportion of patients with intellectual disabilities," Gillissen said.
