Two new genes linked to intellectual disability discovered

Researchers have found two new genes linked to intellectual disability.

In the first study, CAMH Senior Scientist Dr. John Vincent, who heads the MiND (Molecular Neuropsychiatry and Development) Laboratory in the Campbell Family Mental Health Research Institute at CAMH, and his team used microarray genotyping to map the genes of a large Pakistani family which had intermarriage. Five members of the youngest generation were affected with mild to moderate intellectual disability.

Dr. Vincent identified a truncation in the FBXO31 gene, which plays a role in the way that proteins are processed during development of neurons, particularly in the cerebellar cortex.

In the second study, using the same techniques, Dr. Vincent and his team analyzed the genes of two families with intermarriage, one Austrian and one Pakistani, and identified a disruption in the METTL23 gene linked to mild recessive intellectual disability. The METTL23 gene is involved in methylation-a process important to brain development and function.

About one per cent of children worldwide are affected by non-syndromic (i.e., the absence of any other clinical features) intellectual disability, a condition characterized by an impaired capacity to learn and process new or complex information, leading to decreased cognitive functioning and social adjustment.

Although trauma, infection and external damage to the unborn fetus can lead to an intellectual disability, genetic defects are a principal cause.

This type of autosomal recessive gene mutation has traditionally been more difficult to trace, resulting in a paucity of research in this area. Parents of affected children show no symptoms, and the child must inherit one defective copy of the gene from each parent, so that only one in four offspring are likely to be affected.

The two research studies have been published concurrently in the journals Human Genetics and Human Molecular Genetics.