Researchers at the Centre for Addiction and Mental Health (CAMH) and Queen’s University have identified 26 new genes linked to intellectual disability. The study, published online today in Molecular Psychiatry, has implications for the diagnosis and clinical care of those affected, and also adds to our growing knowledge of brain development and functioning. It may eventually lead to personalized treatments for affected individuals. Interestingly, some of the genes identified are thought to be connected with autism spectrum disorders.
More than one in 100 children worldwide are affected by intellectual disability, which is characterized by significant limitations in learning that also affect their day-to-day lives. Frequently, intellectual disability also accompanies symptoms of autism spectrum disorders, and many genes have been found to be shared by the two illnesses.
Intellectual disability is frequently caused by recessive genes, meaning that an affected child gets a defective copy of the gene from each parent. Studying families with this background, and multiple affected individuals, can enable researchers to identify disease genes that would otherwise remain hidden.
The study involved 192 families from Pakistan and Iran with more than one affected family member. This strategy involves various genetic techniques, including microarray genotyping and whole exome sequencing, and studying families with a history of marriage among relatives. The Canadian research team pinpointed mutations related to intellectual disability in half of these 192 families, in 72 different genes. The identification of 26 new genes adds to 11 new genes that the team had previously linked to intellectual disability.
One immediate implication of the study is to prevent future cases of intellectual disability, the researchers note. Unaffected family members and relatives could be genetically screened to see if they carry these mutations, and provided with counselling on the risks of “within family” marriages. A broader goal is to develop diagnostic screening tools that are also relevant to populations in which “within family” marriages are rare, such as Canada, USA, Japan, China and Europe. Ultimately, this information would be used to plan more personalized treatment.
Citation: Harripaul, R., N. Vasli, A. Mikhailov, M. A. Rafiq, K. Mittal, C. Windpassinger, T. I. Sheikh, A. Noor, H. Mahmood, S. Downey, M. Johnson, K. Vleuten, L. Bell, M. Ilyas, F. S. Khan, V. Khan, M. Moradi, M. Ayaz, F. Naeem, A. Heidari, I. Ahmed, S. Ghadami, Z. Agha, S. Zeinali, R. Qamar, H. Mozhdehipanah, P. John, A. Mir, M. Ansar, L. French, M. Ayub, and J. B. Vincent. “Mapping autosomal recessive intellectual disability: combined microarray and exome sequencing identifies 26 novel candidate genes in 192 consanguineous families.” Molecular Psychiatry, 2017. doi:10.1038/mp.2017.60.
Research funding: Canadian Institutes of Health Research
Adapted from press release by Centre for Addiction and Mental Health (CAMH).