Phenotypic spectrum of GNAO1 variants: epileptic encephalopathy to involuntary movements with severe developmental delay

Eur J Hum Genet. 2016 Jan;24(1):129-34. doi: 10.1038/ejhg.2015.92. Epub 2015 May 13.

Abstract

De novo GNAO1 variants have been found in four patients including three patients with Ohtahara syndrome and one patient with childhood epilepsy. In addition, two patients showed involuntary movements, suggesting that GNAO1 variants can cause various neurological phenotypes. Here we report an additional four patients with de novo missense GNAO1 variants, one of which was identical to that of the previously reported. All the three novel variants were predicted to impair Gαo function by structural evaluation. Two patients showed early-onset epileptic encephalopathy, presenting with migrating or multifocal partial seizures in their clinical course, but the remaining two patients showed no or a few seizures. All the four patients showed severe intellectual disability, motor developmental delay, and involuntary movements. Progressive cerebral atrophy and thin corpus callosum were common features in brain images. Our study demonstrated that GNAO1 variants can cause involuntary movements and severe developmental delay with/without seizures, including various types of early-onset epileptic encephalopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Amino Acid Sequence
  • Animals
  • Corpus Callosum / metabolism
  • Corpus Callosum / pathology
  • Developmental Disabilities / diagnosis
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / pathology
  • Dyskinesias / diagnosis
  • Dyskinesias / genetics*
  • Dyskinesias / pathology
  • Electroencephalography
  • Female
  • GTP-Binding Protein alpha Subunits, Gi-Go / genetics*
  • Gene Expression
  • Genotype
  • Humans
  • Infant
  • Molecular Sequence Data
  • Mutation, Missense*
  • Phenotype
  • Sequence Alignment
  • Spasms, Infantile / diagnosis
  • Spasms, Infantile / genetics*
  • Spasms, Infantile / pathology

Substances

  • GNAO1 protein, human
  • GTP-Binding Protein alpha Subunits, Gi-Go

Supplementary concepts

  • Infantile Epileptic-Dyskinetic Encephalopathy