Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/10210
Title: A GABAA receptor mutation causing generalized epilepsy reduces benzodiazepine receptor binding.
Austin Authors: Fedi, Marco;Berkovic, Samuel F ;Marini, Carla;Mulligan, Rachel S ;Tochon-Danguy, Henri;Reutens, David C
Affiliation: Department of Medicine, The University of Melbourne, Austin Health Heidelberg, Victoria, Australia
Issue Date: 27-Jul-2006
Publication information: Neuroimage 2006; 32(3): 995-1000
Abstract: Understanding the consequences of newly discovered single gene mutations causing human epilepsy has the potential to yield new insights into the underlying mechanisms of this disorder. A mutation of the gamma2 subunit of the GABA(A) receptor, which substitutes glutamine for arginine at position 43 (R43Q) has been found in a familial generalized epilepsy. We tested the hypothesis that individuals affected by the GABRG2(R43Q) mutation have reduced binding to the GABA(A) receptor complex using positron emission tomography (PET) and the benzodiazepine receptor ligand [(11)C]-flumazenil. Fourteen subjects with the GABRG2(R43Q) mutation and 20 controls were studied. Benzodiazepine receptor binding was reduced in subjects with the mutation (mean whole brain binding potential for [(11)C]-flumazenil: GABA(A) mutation 0.66+/-0.1; controls 0.89+/-0.1; P<0.003). The greatest change in benzodiazepine binding occurred anteriorly, with peak differences in insular and anterior cingulate cortices revealed by statistical parametric mapping. Our findings provide in vivo evidence of reduced benzodiazepine receptor binding in subjects with the mutation. As synaptic inhibition in the human brain is largely mediated by the GABA(A) receptor, these findings are likely to represent an important clue to the mechanisms linking this gene defect and the epilepsy phenotype.
Gov't Doc #: 16875845
URI: http://ahro.austin.org.au/austinjspui/handle/1/10210
DOI: 10.1016/j.neuroimage.2006.05.059
URL: https://pubmed.ncbi.nlm.nih.gov/16875845
Type: Journal Article
Subjects: Adult
Aged
Brain Mapping
Epilepsy, Generalized.genetics.radionuclide imaging
Female
Flumazenil.metabolism
GABA Modulators.metabolism
Gyrus Cinguli.metabolism.radionuclide imaging
Humans
Image Processing, Computer-Assisted
Magnetic Resonance Imaging
Male
Middle Aged
Mutation.physiology
Positron-Emission Tomography
Receptors, GABA-A.genetics.metabolism
Appears in Collections:Journal articles

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