Abstract
Background: Childhood Absence Epilepsy (CAE) is considered to have a predominantly,
perhaps exclusively, genetic background. To date, genes responsible for susceptibility
to CAE have not been identified. The object of the present study was to test association
between CAE and the genes encoding the γ-aminobutyric acid (GABA) type-A receptor
subunits α5 (GABRA5) and β3 (GABRB3) located on the long arm of chromosome 15 (15q11–q13).
Methods: A family-based candidate gene approach was applied: 50 Austrian nuclear families
ascertained for the presence of an affected child were investigated. GABRA5 and GABRB3
subunit genes were genotyped using DNA gained from peripheral blood samples by Polymerase
Chain Reactions (PCR). Genetic association was tested using a Monte Carlo Version
of the multi-allele Transmission-Disequilibrium Test (TDT).
Results: The TDT displayed significant overall association with GABRB3 (p = .0118).
Conclusions: The present data suggest that the tested polymorphism may be either directly
involved in the etiology of CAE or in linkage disequilibrium with disease-predisposing
sites.
Keywords
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References
- Severe epilepsy in a patient with Prader–Willi syndrome due to a inversion-duplication of chromosome 15q11–13. A clinical, neurophysiological and molecular genetic study (abstract).Epilepsia. 1995; 36: S1
- Genetic aspects of the epilepsies.in: Sakai T Tsuboi T Genetic Aspects of Human Behavior. Igaku-Shoin, Tokyo1985: 129-145
- Developmental changes in human GABAA receptor subunit composition.Ann Neurol. 1993; 34: 687-693
- Duplication of 15q11–13 region in a patient with autism, epilepsy and ataxia.Dev Med Child Neurol. 1994; 36: 736-742
- Proposal for revised classification of epilepsies and epileptic syndromes.Epilepsia. 1989; 30: 389-399
- Myoclonic absence-like seizures and chromosome abnormality syndromes.Epilepsia. 1998; 39: 660-663
- The human γ-aminobutyric acid receptor subunit β3 and α5 in chromosome 15q11–13 is rich in highly polymorphic (CA)n repeats.Genomics. 1994; 19: 157-160
- Structure and organization of GABRB3 and GABRA5.Genomics. 1997; 41: 63-69
- Molecular heterogeneity.Am J Hum Genet. 1993; 53: 22-25
- Angelman Syndrome associated with an inversion of chromosome 15q11.2q24.3.Am J Hum Genet. 1997; 60: 574-580
- Lack of association between juvenile myoclonic epilepsy and GABRA5 and GABRB3 genes.Am J Med Genet. 1997; 74: 150-153
- Linkage analysis vs. association analysis.Am J Hum Genet. 1993; 53: 367-384
- Mice devoid of γ-aminobutyric type A receptor β3 subunit have epilepsy, cleft palate, and hypersensitive behavior.Proc Natl Acad Sci USA. 1997; 94: 4143-4148
- Power studies for the transmission/disequilibrium tests with multiple alleles.Am J Hum Genet. 1997; 60: 691-702
- The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. III. Embryonic and postnatal development.J Neurosci. 1992; 12: 4251-4272
- GABAA receptor channels.Ann Rev Neurosci. 1994; 17: 569-602
- Idiopathic Generalized Epilepsies. John Libbey & Company Ltd, London, GB1994
- Tests for linkage and association in nuclear families.Am J Hum Genet. 1997; 61: 439-448
- A cluster of three GABAA receptor subunit genes is deleted in a neurological mutant of the mouse p locus.Nature. 1993; 364: 448-450
Neubauer BA, Kämpfer F, Fiedler B, Schwabe G, Doose H, Stephani U (1997): Toward the mapping of a gene responsible for rolandic epilepsy (Abstract). Epilepsia 38(suppl 3):201.
- Stargazer.Epilepsy Res. 1990; 7: 129-135
- Targeting epilepsy genes.Neuron. 1996; 16: 24-244
- GABA and epileptogenesis.Epilepsia. 1997; 38: 399-407
- Differential and transient expression of GABAA receptor α-Subunit mRNAs in the developing rat CNS.J Neurosci. 1992; 12: 2888-2900
- The phenotypic spectrum related to the human epilepsy susceptibility gene “EJM1.”.Ann Neurol. 1995; 38: 210-217
- Refinement of map position of the human GluR6 kainate receptor gene (GRIK2) and lack of association and linkage with idiopathic generalized epilepsies.Neurology. 1995; 45: 1713-1720
- Common subtypes of idiopathic generalized epilepsies.Am J Med Genet. 1996; 67: 31-39
- Exclusion of linkage between the idiopathic generalized epilepsies and the GABAA receptor α1 and γ2 subunit cluster on chromosome 5.Epilepsy Res. 1996; 23: 235-244
- Linkage analysis between idiopathic generalized epilepsies and the GABAA receptor α5, β3 and γ3 subunit gene cluster on chromosome 15.Acta Neurol Scand. 1997; 96: 1-7
- Exclusion of linkage between DNA markers in the juvenile myoclonic epilepsy locus of chromosome 6p and childhood absence epilepsy.Epilepsia. 1993; 34: S149
- Multiplicity of GABAA-benzodiazepine receptors.Trends Pharmacol Sci. 1989; 10: 407-411
- Ligand-gated Cl− ion channels modulated by multiple drug binding sites.Trends Pharmacol Sci. 1992; 13: 446-450
- Identification of a putative DNA replication origin in the γ-aminobutyric acid receptor β3 and α5 gene cluster on human chromosome 15q11–13, a region associated with parental imprinting and allele-specific replication timing.Gene. 1996; 173: 171-177
- Basic mechanisms of generalized absence seizures.Ann Neurol. 1995; 7: 77-88
- GABAA receptor impairment in the genetic absence epilepsy rats from Strasbourg (GAERS).Epilepsy Res. 1993; 15: 229-238
- Possible association of a silent polymorphism in the neuronal nicotinic acetylcholine receptor subunit α4 with common idiopathic generalized epilepsies.Am J Med Genet. 1997; 74: 445-449
- Mapping disease genes.Am J Hum Genet. 1995; 57: 487-498
- A novel allosteric modulatory site on GABAA receptor β subunit.Neuron. 1994; 12: 775-782
- Linkage analysis with HLA-DQ A1 and A2 in juvenile myoclonic epilepsy and childhood absence epilepsy.Epilepsia. 1990; 31: 819
- Angelman Syndrome.Am J Med Genet. 1995; 56: 237-238
Article info
Publication history
Accepted:
February 10,
1999
Received in revised form:
February 2,
1999
Received:
July 2,
1998
Identification
Copyright
© 1999 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
