title: GNAO1-associated epileptic encephalopathy and movement disorders: c.607G>A variant represents a probable mutation hotspot with a distinct phenotype.
abstract: We describe a case of GNAO1-associated epilepsy and chorea in a patient with a de novo pathogenic mutation. This patient is unique in being the first reported male with this phenotype, and we propose that this genetic variant may represent a mutation hotspot that characterizes a unique phenotype. This 5.2-years-old boy presented with seizures, chorea, and severe global developmental delay. Brain imaging showed progressive diffuse cerebral atrophy. EEG monitoring revealed multifocal and diffuse discharges, along with generalized-onset seizures. Genetic testing found a de novo pathogenic variant in the GNAO1 gene (c.607G>A; p.Gly203Arg). A review of the literature showed two other patients with similar phenotype and the same genetic variant. In contrast, other patients with neurological involvement had private mutations in the GNAO1 gene. The neurological phenotypes associated with GNAO1 mutations appear to lie on a spectrum, and it is possible that the c.607G>A (p.Gly203Arg) variant characterizes a phenotype with both severe epilepsy and chorea. [Published with video sequence on www.epilepticdisorders.com].
authors.affiliation: Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Ravindra
authors.initials: R
authors.lastname: Arya
authors.affiliation: Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Christine
authors.initials: C
authors.lastname: Spaeth
authors.affiliation: Movement Disorders and Tourette's Syndrome Clinics, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Gilbert
authors.affiliation: Division of Pediatric Neuroradiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Leach
authors.affiliation: Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Katherine D
authors.initials: KD
authors.lastname: Holland
mesh_terms: D001284:Atrophy / Q000473:pathology; D002675:Child, Preschool; D002819:Chorea / Q000235:genetics* / Q000503:physiopathology; D002658:Developmental Disabilities / Q000235:genetics* / Q000503:physiopathology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D012640:Seizures / Q000235:genetics / Q000473:pathology / Q000503:physiopathology
chemical_list: C584143:GNAO1 protein, human; D019206:GTP-Binding Protein alpha Subunits, Gi-Go
keywords: GNAO1; chorea; drug-resistant epilepsy; epilepsy genetics; epileptic encephalopathy