Abstract

THE EARLY INFANTILE EPILEPTIC ENCEPHALOPATHY ASSOCIATED WITH MUTATION IN GABRB3 GENE

T.V. Kozhanova*, S.S. Zhilina, T.I. Mescheryakova, E.G. Lukyanova, E.S. Bolshakova, K.V.Osipova, S.O. Ayvazyan and A.G. Prityko

Abstract

GABRB3 gene, located on chromosome 15q11.2-q12, encodes β3- subunit of the GABAA receptor. The reduced GABRB3 expression underlies in the pathogenesis of absence seizures, abnormal sensory processing, and other neurodevelopmental disorders such as Angelman syndrome, autism spectrum disorders, and intellectual disability. We present clinical case of early epileptic encephalopathy in patient with de novo mutation in the GABRB3 gene, identified by whole-exome sequencing. Similar to previous reported clinical cases, our patient had multiple seizure types resistant to therapy, with a tendency to group into clusters and development of refractory epileptic status, significant delay in psychomotor and pre-speech development. Electroencephalography demonstrated ictal generalized and multifocal epileptiform activity. The novel de novo nucleotide sequence variant in the 7 exon of the GABRB3 gene (c.757C> T, p.Pro253Ser) was detected by whole-exome sequencing and confirmed Sanger sequencing. The our clinical case shows the possibility of the ketogenic diet use in the complex therapy of refractory epileptic status in a patient with a mutation in the GABRB3 gene, that correlates with the world experience in the treatment of epileptic status. The own clinical case shows that mutations in the GABRB3 gene may be the cause of early epileptic encephalopathy and demonstrate the importance of DNA diagnostics using the method of whole-exome sequencing in order to find molecular defect.

Keywords: GABRB3 gene, early epileptic encephalopathy, whole-exome sequencing, ketogenic diet.