MET Receptor Tyrosine Kinase and Autism Spectrum Disorders

MET is a protein that mediates cell functions involved in building brain architecture, and in gastrointestinal repair and immune responses. Based on their discovery of a variant of the MET gene that is associated with autism spectrum disorder (ASD), Dr. Levitt and colleagues hypothesized that alterations in MET function contribute to the brain-based and medical conditions that characterize individuals with ASD. They also hypothesized that environmental factors compound genetic risk by disrupting MET expression. The functional MET variant, which decreases expression of the gene approximately 2-fold, more than doubles the risk of ASD. The investigators determined whether the variant defines individuals with specific medical and behavioral co-occurring conditions. Subjects with ASD and co-occurring medical conditions, such as GI or immune disorders were studied through ASD medical clinics at Vanderbilt and Massachusetts General Hospital . The investigators determined which individuals carry the ASD-associated MET variant, and correlate expression of the MET protein in blood immune cells and when available, in gut biopsies. These subjects and those from the AGRE and Simons collections were subdivided using available behavioral and social scales to determine if the MET variant is found more prevalently with certain traits. Finally, the investigators examined how the MET variant in cells responds following exposure to common environmental toxins, such as dioxin and fertilizers that interfere with gene expression. The hope was that this research program would lead to better means for diagnosing and treating subgroups of ASD patients, and determine how gene-environment may play a role in increasing ASD risk.