Phenome of families with autism and epilepsy

A comprehensive study of the causes of childhood neurodevelopmental disorders (NDDs), such as autism spectrum disorders (ASD) and epilepsy, is becoming more important every year. In this field, the study of Phenome, i.e., a set of measurable characteristics resulting from complex interactions at the level of the genome, methylome, proteome, environment, etc., can help improve our knowledge of NDDs. This study will provide a better understanding of the biological mechanisms of nervous system diseases, which are critical for optimal diagnosis and treatment. Studies on the NDD phenome is still in its infancy. We are just beginning to rethink the causes of NDD based on systemic data that span multiple biological levels. But already, the accumulated data suggest that NDD is a result of the interaction of the genetic profile with a pool of environmental factors.In an integrative functional genomic analysis in multiplex ASD families from Kazakhstan, we identified metabolic pathways and proteins that were not previously associated with ASD. At the same time, some of these proteins have been shown to be associated with epilepsy, confirming that the genetic causes of their occurrence overlap. To gain a more comprehensive understanding of the role of these and other proteins and their genes in the development of the NDD phenotype, in this project we propose to perform whole-exome sequencing (WES) in families with ASD in combination with epilepsy and analyze the correlation of the identified features of the exome with clinical and phenotypic features.The project will allow us to continue active interaction with foundations and rehabilitation centers working on this problem. The results of the project will be of particular interest to both families with NDD and their physicians. In addition to testing our hypothesis, WES suggests that previously unknown mutations in protein-coding sequences as well as metabolic pathways potentially associated with NDD may be discovered.