Individuals with SATB2-associated syndrome have impaired vitamin and energy metabolism pathways.

Special AT-rich sequence-binding protein 2 (SATB2) is a master regulator of gene expression. Mutations of the SATB2 gene results in the SATB2-associated syndrome (SAS), a genetic disorder characterized by neurodevelopmental disabilities and autism-related phenotype. The importance of plasma as an indicator of SAS phenotypes is unknown. We aim to investigate if pathogenic variants in SATB2 are associated with alteration to relevant pathways in the plasma of SAS patients and identify key differentially regulated proteins which may serve as biomarkers to improve diagnostic and future pharmacological approaches. We used well-validated proteomic technologies to determine the proteomic profile of plasma from SAS patients compared to healthy control subjects. Bioinformatical analysis was performed to identify significant proteins and functionally enriched pathways. We identified differentially expressed proteins in the plasma of SAS patients that are significantly involved in metabolism-related pathways. Energy metabolism, glucose metabolism and vitamin metabolism pathways are significantly enriched in SAS patients as compared to healthy controls. Our study linked SATB2 mutations to the impairment of plasma proteins involved in different metabolic pathways in SAS patients.