Autism spectrum disorders (ASD) are due to high heritability, a group of neurodevelopmental conditions in which genetic studies represent a significant diagnostic tool. Within the framework of this research project, we analyzed the exome in Slovenian subjects diagnosed with ASD. Clinically important sequence variants were further described. Variants that were found to have arisen de novo were further analyzed by comparing them with data from the denovo-db database, where all the de novo mutations associated with various neurodevelopmental diseases are collected. We discovered that de novo mutations in Slovenian subjects with ASD occur in genes that are also listed more often in the denovo-db database. Furthermore, intending to discover new variants in connection with ASD, we also performed an analysis with the Orval tool and a gene-based burden analysis with the TRAPD software. By analyzing rare variants in the autism multiplex family with the Orval tool, we discovered two different variants in the ADCY2 and XRCC3 genes, which in combination are expected to be pathogenic. In the following gene-based burden analysis, we discovered a new variant in the PPP2R5D gene, which is expected to be pathogenic. The procedure in both analyses proved suitable for discovering new variants, which we suggest to other researchers. The final analysis of frequent variants showed that the majority of subjects with a primary diagnosis of ASD without associated clinical signs had a higher polygenic risk score (PRS) than the majority of subjects from families with one affected member with similar clinical signs. These results will help advance the understanding of polygenic risk in subjects with ASD.
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