Intractable Rare Dis Res. 2023;12(4):234-240. (DOI: 10.5582/irdr.2023.01092)

Identification of novel and de novo GABRB1 mutation in Chinese patient with developmental and epileptic encephalopathy 45

Zhang S, Wang Y, Liu M, Du Z, Lu Y, Sun P, Han J


Developmental and epileptic encephalopathy 45 (DEE45) is an autosomal dominant disease caused by variation in the gamma-aminobutyric acid type A receptor subunit beta 1 (GABRB1) gene. Affected individuals have severely impaired intellectual development, hypotonia, and other persistent neurological deficits. However, DEE45 is rare; only four infants with DEE45 have been reported worldwide and no case has been reported in China. Confirming a diagnosis of DEE45 is of great significance for guiding further treatment, assessing patient prognosis, and genetic counseling. The clinical characteristics of DEE45 and the medical history of DEE45 patients requires supplementation and clarification. Here, we present the clinical and genetic findings of a 7-year-old girl with DEE45 carrying a novel de novo GABRB1 mutation (c.858_859delinsTT, p.286_287delinsIleSer) identified by whole exome sequencing (WES). The mutation is phylogenetic conserved in the second helix of the β1-subunit's transmembrane region. Western blot and RT-qPCR both indicated significant increase in the expression levels of GABRB1 mutant when compared with wild. The proband has epileptic encephalopathy and experienced refractory epilepsy onset at age 2 months and showed developmental delay at age 8 months. Electroencephalography (EEG) displayed hypsarrhythmia. Magnetic resonance imaging (MRI) showed no significant abnormalities in the internal structure of the patient's brain, which is displayed in two previously reported cases. The patient's symptoms of hypotonia, ataxia, profound mental retardation, and dysmetria became evident with development. In summary, we report the genetic and clinical characteristics of the first Chinese patient with DEE45 and explores the relationship between mutation and clinical symptoms.

KEYWORDS: DEE45, GABRB1, de novo mutation, developmental delay, epilepsy of infancy, electroencephalography

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