Grant: Project Grant

The costs of developmental disorders of cognition and intellectual disability (ID) are enormous. No effective treatments are available for ID and thus there is an urgent need for improved understanding of these disorders. X-linked intellectual disability (XLID) affects 1 to 3 percent of the population and is clinically characterized by a deficit in intellectual function with an intelligence quotient (IQ) of less than 70 before the age of 18. Gene deletions, duplications, inversions and point mutations on the X chromosome have been associated with XLID. The Börjeson-Forssman-Lehmann syndrome (BFLS) was first described as an XLID syndrome by Mats Börjeson and colleagues in 1962. The main clinical features of BFLS become apparent with age. Developmental delay usually appears before the first birthday. All BFLS patients have intellectual disabilities, ranging from mild to severe. Multiple mutations in the PHF6 gene on the X chromosome have been identified in BFLS patients. In this proposal, we will investigate the mechanisms by which impaired PHF6 function drives neurodevelopmental defects and leads to the pathogenesis of BFLS. The results obtained from these studies will be of biological and clinical relevance for better understanding and treatment of neurodevelopmental disorders.