Rare variants in 45 genes account for 25% of cases with NDDs in 415 pediatric patients

Abstract Neurodevelopmental disorders (NDDs) are common conditions including clinically diverse and genetically heterogeneous diseases, such as intellectual disability, autism spectrum disorders, and epilepsy. Understanding the genetic causes of NDDs is challenging due to their complex and heterogeneous nature. In this study, a targeted gene panel sequencing has been used to investigate the genetic causes of NDDs in a cohort of 415 pediatric patients. We identified 60 pathogenic and 49 potentially pathogenic variants in 102 individuals that accounted for 25% of NDD cases in the cohort. The majority of causative variants were de novo, with some inherited from mildly affected parents. Loss-of-function variants were the most common type of causative mutation. In silico analysis tools were used to assess the potential impact of variants on splicing and structural/functional effects of missense variants. The study highlights the challenges in variant interpretation and predicting associated phenotypes. The clinical features observed in some patients were atypical for the mutations found in their genes. Overall, this study provides valuable insights into the genetic causes of NDDs and emphasizes the importance of understanding the underlying genetic factors for accurate diagnosis, prognosis, and intervention development in neurodevelopmental conditions.