Peripheral Markers of the γ-Aminobutyric Acid (GABA)ergic System in Angelman's Syndrome

Abstract

It has recently been demonstrated that patients with Angelman's syndrome who exhibited a deletion on cytogenetic tests show more severe clinical pictures with drug-resistant epilepsy than patients with Angelman's syndrome not carrying the deletion. To verify if this difference in clinical severity can be attributed to genes for the three gamma-aminobutyric acid (GABA)A receptor subunits (GABRB3, GABRA5, GABRG3) located in the deleted region, a possible modification of peripheral markers of the GABAergic system was investigated in 12 subjects with Angelman's syndrome and 20 age-matched subjects (8 with idiopathic epilepsy and 12 not affected by neurologic diseases). The results confirmed a more severe clinical picture, and epilepsy syndrome in particular, in Angelman's syndrome patients with deletions versus patients without deletions. In contrast, biochemical study (based on dosage of plasma levels of GABA and diazepam binding inhibitor, an endogenous ligand of GABAA and peripheral benzodiazepine receptors, showed contradictory results: patients with Angelman's syndrome showed significantly higher levels of GABA and diazepam binding inhibitor than patients without neurologic impairment but significantly lower levels than epileptic controls.

mRNA and Protein Levels for GABAAα4, α5, β1 and GABABR1 Receptors are Altered in Brains from Subjects with Autism

“…There hasn't been a connection established between any of the GABA receptors examined in the current study with Fragile X syndrome. Deletion of the 11.2-q13 region of chromosome 15, where the GABRα5 gene is located, has been associated with a more severe clinical picture of Angelman Syndrome (Borgatti et al, 2003). However, this is likely due to the presence of ubiquitin protein ligase E3A (UBE3A) in this region (Matsuura et al, 1997).…”

Epilepsy in Angelman syndrome: A scoping review

“…Due to characteristic presence of intractable seizures and EEG changes associated with AS, initial research on pathogenesis was focused on GABA(the principal inhibitory neurotransmitter in the cortex) that maintains inhibitory tone in the brain and counterbalances excitatory glutamatergic outputs [6,7]. GABA mediates its action via GABA receptors, which composed of 5 subunits.…”