Grant: Project Grant

Intellectual disability (ID) affects 2 to 3% of the population worldwide, and in Canada, 7,700 to 11,570 children with ID are born every year. ID places an enormous burden on affected individuals and their families, the health care system, and society. The lifetime costs to care for a person with ID is ~US$1,000,000. ID has many different causes, and optimal clinical management requires the identification of the specific cause in each affected individual. Whole-genome sequencing (WGS), an advanced genetic test that scans the entire DNA sequence of an individual, identifies mutations in more than half of patients with moderate to severe forms of ID. However, although WGS is an excellent test for some types of mutations, it cannot detect all of them, and the cause is not found in nearly one-third to one-half of the patients with a presumed genetic form of ID who undergo WGS. The goal of this project is to employ state-of-the-art genomic technology with an optimized data analysis framework to identify the genetic cause in at least 25% of the 60 families with moderate to severe ID who have strong clinical evidence of a genetic cause (e.g., similarly affected sibs or characteristic features of a recognized genetic syndrome) but in whom WGS has not revealed a causal mutation. All identified ID-causing mutations will be independently validated and returned to the patients and their families, and all computational tools developed through this project will be made freely available for use by scientists and physicians throughout the world. By developing methods to identify previously-unrecognized disease-causing mutations among patients with ID, we aim to improve our understanding of ID and enhance the care of affected patients and their families.