2017•Journal of NeurogeneticsOpen access
Expanding the phenotypic spectrum ofGABRG2variants: a recurrentGABRG2missense variant associated with a severe phenotype
Fanggeng Zou, Kirsty McWalter, Lindsay Schmidt, Amy Decker, Jonathan Picker, Sharyn A. Lincoln, David A. Sweetser, Lauren C. Briere, Chellamani Harini, Members of the Undiagnosed Diseases Network, Eric D. Marsh, Līvija Medne, Raymond Wang, Karen Leydiker, Andrew Mower, Gepke Visser, Inge Cuppen, Koen L.I. van Gassen, Jasper van der Smagt, Adeel Yousaf, Michael B. Tennison, Anita Shanmugham, Elizabeth Butler, Gabriele Richard, Dianalee McKnight
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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.