Systematic Re-evaluation and Classification of Syndromic Genes Associated with Autism Spectrum Disorder
Sarada Giridharan
Mentor: Dr. Eric Larsen, Senior Scientist, MindSpec, Inc.
Date/Time: August 22nd, 2025 at 11:45 AM.
Abstract: Autism spectrum disorder (ASD) has a strong genetic basis, with some of the initial evidence coming from the discovery of monogenic syndromes in which a subset of affected individuals was diagnosed with ASD or presented with ASD-related features in addition to recurrent comorbid congenital anomalies. More recently, the utilization of whole exome and whole genome sequencing in ASD cohorts has enabled the identification of hundreds of candidate genes, some of which have been subsequently associated with neurodevelopmental syndromes of their own. This project focuses on the systematic re-evaluation of 197 genes classified as syndromic in AutDB, a curated database for collection, annotation and visualization of genes for autism. Utilizing optimized literature searches across PubMed, Google Scholar, and AutDB entries, each gene was re-assessed for syndromic status with respect to ASD based on tiered levels of literature evidence (Support_A/B/C/Review). Genes determined to be syndromic were further classified into clinically-defined/phenotype-first (Type 1) or molecularly-defined/genotype-first (Type 2) categories. Classification criteria included TADA statistical significance, cohort size, diagnostic methods, and the strength of published evidence.
Several genes were excluded following re-evaluation, reflecting limitations in OMIM-based syndrome assignment and emphasizing the importance of rigorous evidence-based review. A subset of 25 genes, identified as high-priority due to robust support in key publications (Fu et al. 2022, Zhou et al. 2022), underwent in-depth analysis including evidence tracking, timeline curation, and standardized HPO-based phenotypic profiling. This work contributes to the refinement of syndromic ASD gene classification and enhances the utility of AutDB for future ASD research.