[11C]Flumazenil positron emission tomography analyses of brain gamma-aminobutyric acid type a receptors in Angelman syndrome

Objective To evaluate the role of the gamma-aminobutyric acid type A (GABA(A)) receptor in Angelman syndrome (AS). Study design We performed [C-11]flumazenil positron emission tomography (PET) and examined GABA(A) receptor expression in 7 patients with AS of various genotypes (5 with the deletion, 1 with an imprinting defect [1D], and 1 with a UBE3A mutation) and 4 normal control healthy volunteers. Results Relative to the control subjects, the [C-11]flumazenil binding potentials (BPs) were significantly higher in the cerebral cortex and cerebellum in the 5 patients with the deletion and in the 1 patient with a UBE3A mutation, and were less frequently or barely increased in adult patients with the deletion and in the patient with 1Ds. Conclusions Total GABA(A) receptor expression was increased in patients with AS with various genotypes. We suggest that a developmental dysregulation of the GABA(A) receptor subunits occurs in patients with AS.