biostudies-literatureUnknown13(2)Dainelli A<h4>Background</h4>RALA is a small GTPase from the RAS superfamily implicated in signal transduction and cytoskeletal dynamics. Recently, de novo variants in RALA have been associated with a neurodevelopmental syndrome characterized by intellectual disability (ID), developmental delay (DD), and seizures. So far, only < 12 patients have been reported.<h4>Methods</h4>In this study, we report two novel patients with neurodevelopmental impairment and epilepsy carrying previously unreported RALA variants. We performed a thorough clinical investigation of these patients and performed brain MRI to detect potential abnormalities. Trio-exome sequencing and/or NGS panel testing were conducted to identify the genetic variants. Then, we reviewed previous cases reported in the literature.<h4>Results</hMolecular genetics & genomic medicinee70072https://www.ebi.ac.uk/biostudies/studies/S-EPMC11803908biostudies-literatureNovel De Novo RALA Missense Variants Expand the Genotype Spectrum of Hiatt-Neu-Cooper Neurodevelopmental Syndrome.PMC11803908Dainelli ACapra VMancardi MMNosrati MSSRomano FVercellino FNigro VZara FScala MTorella AfalseNovel De Novo RALA Missense Variants Expand the Genotype Spectrum of Hiatt-Neu-Cooper Neurodevelopmental Syndrome.<h4>Background</h4>RALA is a small GTPase from the RAS superfamily implicated in signal transduction and cytoskeletal dynamics. Recently, de novo variants in RALA have been associated with a neurodevelopmental syndrome characterized by intellectual disability (ID), developmental delay (DD), and seizures. So far, only < 12 patients have been reported.<h4>Methods</h4>In this study, we report two novel patients with neurodevelopmental impairment and epilepsy carrying previously unreported RALA variants. We performed a thorough clinical investigation of these patients and performed brain MRI to detect potential abnormalities. Trio-exome sequencing and/or NGS panel testing were conducted to identify the genetic variants. Then, we reviewed previous cases reported in the literature.<h4>Results</h2025-01-01T00:00:00Z2025 Feb2026-06-01T15:04:32.804Z2025-04-06T07:42:48.893ZS-EPMC118039083991838210.1002/mgg3.70072