부산대학교 도서관

PURPOSE OF STUDY: Current research supports an interaction between genetic events and environmental stressors in the aetiology of Autism Spectrum Disorder (ASD). There is an enrichment of mutations to genes involved in the β-Catenin pathway, which influences formation of the blood brain barrier (BBB). The BBB excludes antibodies from the brain. Research suggests that maternal autoimmunity increases ASD risk due to the production of brain-reactive antibodies that can cross the placenta and access the brain prior to BBB formation, impacting fetal neurodevelopment. We examined the interactive effect of gene mutations impacting the β-Catenin pathway and maternal autoimmunity on ASD severity. METHODS USED: Participants included 2759 children with ASD from the Simons Simplex Collection for whom whole exome sequencing, phenotypic characterisation, and medical history were completed. Of this sample, 425 children were selected and grouped based on mutations within the β-Catenin pathway vs outside this pathway, and presence vs absence of a history of maternal autoimmunity. ASD associated symptoms across social, communication, and behavioural domains were extracted from clinician interviews and parent questionnaires. Two-way ANOVAs were conducted to evaluate effects of mutations in the β-Catenin pathway and maternal autoimmunity on ASD symptom severity. SUMMARY OF RESULTS: Children with gene mutations in the β-Catenin pathway had more severe repetitive behaviour symptoms than children with mutations outside this pathway (p=0.005). A significant interaction was identified indicating that children with mutations in the β-Catenin pathway and a history of maternal autoimmunity show greater ASD severity (p=0.011). CONCLUSIONS: These findings suggest that mutations to genes involved in BBB development, when combined with a history of maternal autoimmunity, are associated with increased autistic symptomatology. Our results build on prior work that has shown an association between maternal autoimmunity and ASD as well as the interaction between immune system functioning and mutations and ASD clinical presentation. These observations advance our understanding of the causal mechanisms for this multifactorial disorder.