Expanding the phenotypic spectrum of GABRG2 variants: a recurrent GABRG2 missense variant associated with a severe phenotype |
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Authors: | Fanggeng Zou Kirsty McWalter Lindsay Schmidt Amy Decker Jonathan D Picker Sharyn Lincoln |
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Institution: | 1. GeneDx, Inc, Gaithersburg, MD, USA;2. Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA;3. NIH Common Fund, Undiagnosed Diseases Network, Bethesda, MD, USA |
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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. |
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Keywords: | Epilepsy genetics seizures GABRG2 phenotype missense |
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