Résumé
Neurodevelopmental Disorders (NDDs) are constantly increasing, reaching a prevalence of 5% in France in 2021. Better identification of the aetiologic factors of NDDs is important to give answers to the patients and their parents and to improve therapeutic management. Many genes have already been identified as a cause of NDDs, and with the development of high-throughput sequencing, many new variants are discovered and classified as Variant of Uncertain Significance (VUS). TRIO is a novel risk gene associated with NDDs, especially Intellectual Disability (ID) and Autism Spectrum Disorder (ASD), with a genotype-phenotype correlation targeting two functional domains.Here we report a cohort of 12 patients carrying TRIO variants classified as VUS. We analysed the combined phenotypical and functional data to assess whether the variants could be re-classified as either likely pathogenic or likely benign.The results of our study didn’t show a clinical correlation between the phenotypes of VUS carriers and the phenotypes associated with TRIO pathogenic variants. Functional experiments performed on TRIO main function showed no significant impact with respect to catalytic activity and cell phenotypes. This work is a first step towards a reclassification in the “likely benign” category of TRIO VUS presented in our study. It emphasizes the need for further investigation on the functional impact of TRIO and for the integrative approach of patients suffering from NDDs.