Characterisation of De Novo Mutations in Children with Autism Spectrum Disorder in South West Nigeria Using Whole Exome Sequencing

Autism spectrum disorder (ASD) is a neurodevelopmental condition with high heritability, and de novo mutations in synaptic and chromatin-remodelling genes have been identified as major contributors in clinically affected children. While ASD prevalence studies have been conducted in Nigeria, molecular characterisation of de novo mutations in affected Nigerian children remains a significant research gap. This study characterised de novo mutations in children with ASD in South West Nigeria using whole exome sequencing (WES). Thirty trio families (affected child plus both biological parents) were recruited from autism diagnostic and support centres in Lagos, Ogun, and Oyo States. High-quality genomic DNA was extracted and subjected to targeted exome capture followed by 150 base pair paired-end Illumina sequencing. Variant calling, annotation, and de novo identification were performed using GATK, ANNOVAR, and family-based filtering pipelines. Candidate de novo variants were prioritised based on known ASD gene lists, OMIM pathogenic classifications, and in silico functional predictions. Pathogenic or likely pathogenic de novo variants were identified in approximately 15 percent of trios, with genes including SHANK3, ADNP, and CHD8 implicated. This study establishes the first whole exome de novo mutation profile for ASD in South West Nigeria. Keywords: autism spectrum disorder, de novo mutations, whole exome sequencing, South West Nigeria, trio study