Expanding the phenotypic spectrum of GABRG2 variants: a recurrent GABRG2 missense variant associated with a severe phenotype

J Neurogenet. Mar-Jun 2017;31(1-2):30-36. doi: 10.1080/01677063.2017.1315417. Epub 2017 May 2.

Abstract

Pathogenic missense and truncating variants in the GABRG2 gene cause a spectrum of epilepsies, from Dravet syndrome to milder simple febrile seizures. In most cases, pathogenic missense variants in the GABRG2 gene segregate with a febrile seizure phenotype. In this case series, we report a recurrent, de novo missense variant (c0.316 G > A; p.A106T) in the GABRG2 gene that was identified in five unrelated individuals. These patients were described to have a more severe phenotype than previously reported for GABRG2 missense variants. Common features include variable early-onset seizures, significant motor and speech delays, intellectual disability, hypotonia, movement disorder, dysmorphic features and vision/ocular issues. Our report further explores a recurrent pathogenic missense variant within the GABRG2 variant family and broadens the spectrum of associated phenotypes for GABRG2-associated disorders.

Keywords: Epilepsy; GABRG2; genetics; missense; phenotype; seizures.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / pathology*
  • Adolescent
  • Child
  • Epilepsy / genetics
  • Epilepsy / pathology
  • Female
  • Humans
  • Infant
  • Intellectual Disability / genetics
  • Intellectual Disability / pathology
  • Male
  • Motor Disorders / genetics
  • Motor Disorders / pathology
  • Movement Disorders / genetics
  • Movement Disorders / pathology
  • Muscle Hypotonia / genetics
  • Muscle Hypotonia / pathology
  • Mutation, Missense*
  • Pedigree
  • Phenotype
  • Receptors, GABA-A / genetics*
  • Severity of Illness Index*
  • Speech Disorders / genetics
  • Speech Disorders / pathology

Substances

  • GABRG2 protein, human
  • Receptors, GABA-A