A new study jointly led by Queen’s University’s Professor Muhammad Ayub and Professor John Vincent from the Centre for Addiction and Mental Health (CAMH) and has identified 26 new genes linked to intellectual disability. Currently the majority of intellectual disability patients receive no molecular diagnosis, which significantly affects their health and shortens their lifespan.

The study has implications for the diagnosis and clinical care of those affected, and also adds to the growing knowledge of brain development. It also may eventually lead to personalized treatments for affected individuals. Several of the genes identified are also thought to be connected with autism spectrum disorders.

 “Developments in technology and our strategic advantage of access to families from consanguineous populations made this big study possible,” says Dr. Ayub, who also works with the Development Disabilities Consulting Program at Queen’s University. “It is a significant step in the long journey to discoveries that could change our treatment for intellectual disabilities.”

The study involved 192 families from Pakistan and Iran with more than one family member who had an intellectual disability. About one in 100 children worldwide are affected by intellectual disability, which is characterized by significant limitations in learning that also affect daily functioning. Intellectual disability also frequently 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. The families in the study all had a history of marriage among relatives, which occurs quite commonly in communities in South Asia, the Middle East and Africa. This background increases the likelihood that recessive illnesses may occur. Families with such a background and with multiple affected individuals can enable researchers to identify disease genes that would otherwise remain hidden.

Drs Vincent and Ayub along with the Canadian research team pinpointed mutations in 72 different genes related to intellectual disability in half of these 192 families. The identification of 26 new genes adds to 11 genes that the team has previously linked to intellectual disability among these families.

“For the participating families’ future cases of intellectual disability can be prevented by genetic screening of unaffected family members and relatives and focused advice on the risks of ‘within family’ marriages. For cultural reasons this would need to be done with great degree of sensitivity,” says Dr Ayub.

A broader goal in identifying genetic mutations is to develop diagnostic screening tools that are also relevant to populations in which ‘within family’ marriages are rare, such as Canada, United, Japan, China, and Europe. These screens would allow physicians to identify what exactly, at the molecular level, is leading to the condition and symptoms, and to use this information to plan more personalized treatment.

“The genes we have identified will be further studied for their role in development of brain and how their derangement leads to intellectual disability and other brain disorders,” says Dr. Ayub.

The study was published in Molecular Psychiatry.