Decreased binding of [11C]flumazenil in Angelman syndrome patients with GABA(A) receptor beta3 subunit deletions.
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.
Holopainen
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Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland. irma.holopainen@utu.fi
Metsähonkala
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Kokkonen
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Parkkola
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Manner
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Någren
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Korpi
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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
D011963:Receptors, GABA-A