A novel USP51 variant in a patient with autism spectrum disorder and epilepsy

Abstract Background Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder characterized by impaired social communication and repetitive behaviours. The genetic basis of ASD is complex and involves both rare variants with large effect sizes and common variants with small effect sizes. Case presentation This case report describes a 19-year-old male with ASD, intellectual disability, absent speech, and epilepsy. Molecular testing revealed a novel maternally inherited variant in the USP51 gene, which encodes Ubiquitin Specific Peptidase 51, a deubiquitinating enzyme involved in the DNA damage response. Conclusions Based on current knowledge, the variant is predicted to result in a truncated protein and is considered a variant of uncertain significance (VUS). The USP51 gene has been implicated in neurodevelopment, and its role in the developing brain suggests its potential relevance to ASD. Further studies are needed to establish the association of USP51 variants with ASD and elucidate the full phenotypic spectrum associated with these variants.