title: Decreased binding of [11C]flumazenil in Angelman syndrome patients with GABA(A) receptor beta3 subunit deletions.
abstract: We used positron emission tomography (PET) to study brain [11C]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 gamma-aminobutyric acidA/benzodiazepine (GABA(A)/BZ) receptor, whereas Patient 4 had a mutation in the ubiquitin protein ligase (UBE3A) saving the beta3 subunit gene. [11C]FMZ binding potential in the frontal, parietal, hippocampal, 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 reduced number of GABA(A)/BZ receptors, which could partly explain the neurological deficits of the AS patients.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland. irma.holopainen@utu.fi
authors.forename: I E
authors.initials: IE
authors.lastname: Holopainen
authors.forename: E L
authors.initials: EL
authors.lastname: Metsähonkala
authors.forename: H
authors.initials: H
authors.lastname: Kokkonen
authors.forename: R K
authors.initials: RK
authors.lastname: Parkkola
authors.forename: T E
authors.initials: TE
authors.lastname: Manner
authors.forename: K
authors.initials: K
authors.lastname: Någren
authors.forename: E R
authors.initials: ER
authors.lastname: Korpi
mesh_terms: D000293:Adolescent; D000328:Adult; D017204:Angelman Syndrome / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D011963:Receptors, GABA-A / Q000235:genetics*; D014055:Tomography, Emission-Computed
chemical_list: D011963:Receptors, GABA-A