Researchers have discovered 15 genes that play a role in the development of intellectual disabilities. Intellectual disabilities are often caused by a mutation that damages a gene responsible for protein production in cells thus preventing the associated protein from functioning properly.
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. 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.
A de novo mutation is a genetic alteration that is present for the first time in one family member as a result of a variant (or mutation) in a germ cell (egg or sperm) of one of the parents, or a variant that arises in the fertilized egg itself during early embryogenesis.
The results of the study, published in the American Journal of Human Genetics, showed 15 genes in which mutations cluster closely together, 12 of which were associated with developmental disorders. “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, the geneticist from Radboud University in Netherlands.
“We also found three new genes that are likely to play a role in the development of intellectual disabilities as well,” Gilissen added. 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,” Gilissen 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.”