A de novo mutation in RAB11A is associated with neurodevelopmental disorder accompanied by variable multisystem abnormalities

Le résumé fourni par la source

Introduction RAB11A, a Rab GTPase, is crucial for intracellular transport and recycling. Recently, RAB11A mutations have been found to be associated with neurodevelopmental disorders in cohorts. At present, there are still no effective treatment methods for NDDs caused by RAB11A deficiency, thus, identifying pathogenic mutations and generating disease models is crucial for advancing our understanding of these conditions. Methods We analyzed the clinical presentation of a 4-year and 4-month-old boy with a de novo RAB11A mutation c.370A>G. To examine the consequences of RAB11A mutation during early embryonic development, we disrupted the homologous rab11a gene using CRISPR/Cas9 in zebrafish. Results The affected boy who exhibited intellectual disability showed phenotypic features including cerebral atrophy, obesity, motor disability and abnormal muscle tone. Protein structure predictions indicated that RAB11A mutation affected protein stability and enzymatic activity. CRISPR/Cas9-mediated rab11a deficiency in zebrafish larvae significantly reduced brain, forebrain, and midbrain size. Conclusion Our study collectively demonstrated that the RAB11A mutation c.370A>G is associated with neurodevelopmental disorders, characterized by motor deficits and brain anomalies. Additionally, we have successfully developed a zebrafish model to recapitulate these neurodevelopmental disorders associated with RAB11A deficiency, offering a valuable genetic resource for further investigation into this disease.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.