A new study by GNAO1 variants associated with severe childhood speech disorder (Larasati et al., 2026) expands our understanding of the genetic basis of severe childhood speech disorders, including ch...

From Organic Traffic to Billion-Dollar Valuation: The aéPiot Case Study in the Semantic Web Era A Comprehensive Business Analysis of Plat...

Discover how GNAO1 Gene Defect and Epilepsy in Children impact movement disorders and learn about potential treatments and research findings.

Mutations in the GNAO1 gene, which encodes for Go, a major neuronal G protein, are associated with neurodevelopmental disorders, epilepsy, and movement disorders. We identified and characterized a spontaneous heterozygous GNAO1 E246K mutation in an Israeli female infant with complex developmental delays and substantial motor difficulties. This mutation has been reported in other cases as a prevalent pathogenic mutation in patients with motor dysfunction and a broad range of neurological outcomes. To investigate the molecular and functional consequences of the Go E246K mutation, we employed structural modeling and analysis, biochemical assays, mass spectrometry-based proteomics, and cellular functional assays. We show that this mutation does not affect nucleotide binding, nor basal or RGS-accelerated GTP hydrolysis. Despite the E246 position located within a predicted effector binding region, proteomics analysis did not identify any new cellular partners. Instead, we demonstrate that the E246K mutation disrupts the Go regulatory GTPase cycle by directly impairing G{beta}{gamma} dissociation. This impairment overrides the presence of wild-type Go, explaining the dominant effect of the severe neurogenetic phenotype in the heterozygous background. These findings establish a new molecular mechanism for a GNAO1 mutation with dominant-negative effects on the GTPase regulatory cycle. The insights gained from studying this mechanism of action provide a basis for developing specific and personalized therapeutic strategies based on the outcome of a missense mutation in GNAO1.

“She doesn’t quit, so we can’t,” said Jackie Dembishack, mother of 4-year-old Olivia, of Cumberland.

“She doesn’t quit, so we can’t,” said Jackie Dembishack, mother of 4-year-old Olivia, of Cumberland.

Villabona-Amasako Trikuharri mendi lasterketan parte hartzaile berezia izango da aurten: Markel Carmona urnietarra. Gurpil bakarreko aulki baten gainean egingo du lasterketa motza, 12 kilometrokoa,...

El mercadillo solidario de los alumnos de cuarto de la ESO del IES Marqués de Lozoya logró recaudar 1.500 euros para la Asociación GNAO1 España.

La campaña 'El viaje de Nica' busca sensibilizar y conseguir recursos que permitan incrementar la tasa de diagnóstico

Development of an AAV-RNAi strategy to silence the dominant variant GNAO1 c.607G>A linked to encephalopathy  Nature

La Cofradía de Santa Águeda de Cuéllar ha dado a conocer la programación que ha preparado con motivo de la festividad de Santa Águeda en la villa.