This project aims to investigate the genetic factors underlying individual differences in cognitive functioning in people with Williams syndrome.
Williams syndrome (WS) is a rare neurodevelopmental disorder caused by a hemizygous deletion of approximately 26 genes on chromosome 7. Individuals with WS present a distinctive cognitive and behavioral profile characterized by mild to moderate intellectual disability, marked strengths and weaknesses across cognitive domains, unusually high sociability, and elevated anxiety. Although the genetic cause of WS is well established, considerable variability exists in the cognitive phenotype, and the mechanisms responsible for these individual differences remain largely unknown.
Our project aims to identify the genetic factors that contribute to this phenotypic variability through three complementary approaches. First, comprehensive neuropsychological assessments will be used to establish detailed cognitive profiles and identify behavioral characteristics associated with dysfunction of specific brain systems. Second, genomic analyses will examine the contribution of the size and parental origin of the deletion, as well as allelic variation in the remaining copy of genes within the Williams syndrome critical region. Finally, whole-genome analyses will investigate the influence of rare genetic variants elsewhere in the genome by comparing individuals with WS and their parents.
By integrating detailed cognitive phenotyping with state-of-the-art genomic analyses, this research will provide new insights into the genotype–phenotype relationships underlying Williams syndrome. The findings will improve our understanding of the biological mechanisms responsible for cognitive variability and may ultimately contribute to the development of more personalized therapeutic interventions.
Associations
- Autour des Williams, France
- Fédération Williams France
- Syndrome de Williams Suisse
