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

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

Author information

1
a GeneDx, Inc , Gaithersburg , MD , USA.
2
b Division of Genetics and Genomics , Boston Children's Hospital , Boston , MA , USA.
3
c NIH Common Fund , Undiagnosed Diseases Network , Bethesda , MD , USA.
4
d Department of Medical Genetics , Massachusetts General Hospital for Children , Boston , MA , USA.
5
e Division of Neurophysiology , Boston Children's Hospital , Boston , MA , USA.
6
f Division of Child Neurology, Departments of Neurology and Pediatrics , Children's Hospital of Philadelphia , Philadelphia , PA , USA.
7
g Individualized Medical Genetics Center, Division of Human Genetics, Division of Neurology , The Children's Hospital of Philadelphia , Philadelphia , PA , USA.
8
h Division of Metabolic Disorders , CHOC Children's Hospital , Orange , CA , USA.
9
i Neurology , CHOC Children's Hospital , Orange , CA , USA.
10
j Wilhelmina Children's Hospital/University Medical Center , Utrecht , the Netherlands.
11
k Department of Genetics , University Medical Center Utrecht , Utrecht , the Netherlands.
12
l University of North Carolina at Chapel Hill , Chapel Hill , NC , USA.
13
m University of North Carolina at Chapel Hill , Chapel Hill , NC , USA.

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 (c0.316ā€‰Gā€‰>ā€‰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

PMID:
28460589
PMCID:
PMC6169784
DOI:
10.1080/01677063.2017.1315417
[Indexed for MEDLINE]
Free PMC Article

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