Exome Study of Single Nucleotide Variations in Patients with Syndromic and Non-Syndromic Autism Reveals Potential Candidate Genes for Diagnostics and Novel Single Nucleotide Variants

Autism spectrum disorder (ASD) is a neurodevelopmental impairment that occurs due to mutations related to the formation of the nervous system, combined with the impact of various epigenetic and environmental factors. This necessitates the identification of the genetic variations involved in ASD pathogenesis. We performed whole exome sequencing (WES) in a cohort of 22 Bulgarian male and female individuals showing ASD features alongside segregation analyses of their families. A targeted panel of genes was chosen and analyzed for each case, based on a detailed examination of clinical data. Gene analyses revealed that specific variants concern key neurobiological processes involving neuronal architecture, development, and function. These variants occur in a number of genes, including <i>SHANK3</i>, <i>DLG3</i>, <i>NALCN</i>, and <i>PACS2</i> which are critical for synaptic signaling imbalance, <i>CEP120</i> and <i>BBS5</i> for ciliopathies, <i>SPTAN1</i> for spectrins structure, <i>SPATA5</i>, <i>TRAK1</i>, and <i>VPS13B</i> for neuronal organelles trafficking and integrity, <i>TAF6</i>, <i>SMARCB1</i>, <i>DDX3X</i>, <i>MECP2</i>, and <i>SETD1A</i> for gene expression, <i>CDK13</i> for cell cycle control, <i>ALDH5A1, DPYD</i>, <i>FH</i>, and <i>PDHX</i> for mitochondrial function, and <i>PQBP1</i>, <i>HUWE1</i>, and WDR45 for neuron homeostasis. Novel single nucleotide variants in the <i>SPATA5</i>, <i>CEP120</i>, <i>BBS5, SETD1A</i>, <i>TRAK1</i>, <i>VPS13B</i>, and <i>DDX3X</i> genes have been identified and proposed for use in ASD diagnostics. Our data contribute to a better understanding of the complex neurobiological features of autism and are applicable in the diagnosis and development of personalized therapeutic approaches.