• cognitive impairment;
  • diagnostics;
  • exome;
  • exome sequencing;
  • intellectual disability;
  • mental retardation;
  • next-generation sequencing;
  • rare disease

Topper S, Ober C, Das S. Exome sequencing and the genetics of intellectual disability.

Exome sequencing has greatly impacted the speed at which new disease genes are identified. In the last year alone, six studies have used exome sequencing to identify new genes involved in intellectual disability, a genetically heterogeneous condition affecting 1–3% of the population. These studies encompass the full gamut of modes of inheritance and phenotypic presentation, including syndromic and non-syndromic conditions, sporadic and familial cases, and dominant and recessive inheritance patterns. Because different disease presentations require different approaches to gene discovery, studies of intellectual disability provide a nearly comprehensive showcase of strategies for exome-driven gene discovery. Despite these successes, the etiology of ∼60% of cases of intellectual disability remains unknown. The application of exome sequencing to the clinical diagnosis of intellectual disability in the near future will ultimately reduce the number of idiopathic cases and provide a rich source of sequence variation for the identification of new intellectual disability genes.