Decreased binding of [C-11]flumazenil in Angelman syndrome patients with GABA(A) receptor beta(3) subunit deletions

We used positron emission tomography (PET) to study brain [C-11]flumazenil (FMZ) binding in four Angelman syndrome (AS) patients. Patients 1 to 3 had a maternal deletion of 15q11-q13 leading to the loss of beta3 subunit of ga mma -aminobutyric acid(A)/benzodiazepine (GABA(A)/BZ) receptor, whereas Pat ient 4 had a mutation in the ubiquitin protein ligase (UBE3A) saving the be ta (3) subunit gene. [C-11]FMZ binding potential in the frontal, parietal, pocampal, and cerebellar regions was significantly lower in Patients 1 to 3 than in Patient 4, We propose that the 15q11-q13 deletion leads to a reduc ed number GABA(A/)BZ receptors, which could partly explain the neurological deficits of the AS patients.