학술논문

Expanding the phenotypic spectrum of GABRG2 variants: a recurrent GABRG2 missense variant associated with a severe phenotype
Document Type
article
Source
Journal of Neurogenetics. 31(1-2)
Subject
Biological Sciences
Biomedical and Clinical Sciences
Genetics
Brain Disorders
Epilepsy
Neurodegenerative
Neurosciences
Aetiology
2.1 Biological and endogenous factors
Abnormalities
Multiple
Adolescent
Child
Female
Humans
Infant
Intellectual Disability
Male
Motor Disorders
Movement Disorders
Muscle Hypotonia
Mutation
Missense
Pedigree
Phenotype
Receptors
GABA-A
Severity of Illness Index
Speech Disorders
genetics
seizures
GABRG2
phenotype
missense
Members of the Undiagnosed Diseases Network
Clinical Sciences
Neurology & Neurosurgery
Language
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.