Project 467360

Genetic changes affecting the copy number of chromosome 15q13.3 have been linked to a group of rare neurodevelopmental conditions including developmental delay, intellectual disability, autism spectrum disorder, epilepsy, schizophrenia, and others. The critical region contains approximately 10 genes. Treatments are limited and are constrained to targeting the core symptoms over the underlying etiology. . Further, not each person harboring a 15q13.3 copy number change will manifest disease, and the severity and clinical diagnosis is difficult to predict. This represents a significant challenge in determining the health outcomes and counseling of families. To improve clinical diagnostics, we are using a multifaceted approach with an international team of clinicians and scientists. First, we are using an emerging genetic sequencing technique (long-read sequencing) that will help to resolve the complete genetic details of the 15q13.3 CNV region. In addition, we will clinically examine patients using brain electroencephalogram (EEG) testing to identify a 15q13.3 CNV signature and improve diagnostic tools. Finally, our team has access to experimental animal and 3D human stem cell models of the 15q13.3 CNV that will help to understand the developmental course of the brain disorder, and reveal biomarkers to help identify disease progression. The outcome of our 15q13.3 CNV project will be a better understanding of the biological basis of disease, diagnostic tools to predict disease severity, and information to help clinicians in the management of affected individuals.