Abstract
An Ala322Asp mutation in theGABRA1 gene was recently reported to be responsible for causing the autosomal dominant (AD) form of juvenile myoclonic epilepsy (JME) in a French-Canadian family. To study if JME families from India exhibiting the AD mode of inheritance carry the Ala322Asp mutation, we examined 35 unrelated JME-affected individuals from such families for the Ala322Asp mutation inGABRA1. Ala322Asp mutation was not observed in any of these JME-affected individuals, suggesting that this mutation is unlikely to be a predominant mutation involved in causation of epilepsy. To evaluate the possibility of other mutation(s) in and aroundGABRA1 that may predispose to JME, we compared the allele frequencies at two marker loci, D5S2118 and D5S422, flankingGABRA1, in probands and 100 matched population controls. One of the allele frequencies at D5S422 shows a significant difference between the cases and controls (χ2 = 11.44, d.f. = 1,P = 0.0007), suggesting genetic association between JME and genes located in the proximity of the DNA marker.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bata L., Mitchell W., Williamson M., Altahan A., Obeid T., Rees M.et al. 2000 Molecular genetic analysis of juvenile myoclonic epilepsy in the Saudi Arabian population.Epilepsia 41 (suppl. 7), 72.
Commission on Classification and Terminology of the International League Against Epilepsy 1989 Proposal for revised classification of epilepsies and epileptic syndromes.Epilepsia 30, 389–399.
Cossette P., Liu L., Brisebois K., Dong H., Lortie A., Vanasse M.et al. 2002 Mutation ofGABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy.Nat. Genet. 31, 184–189.
Durner M., Sander T., Greenberg D. A., Johnson K., BeckMannagetta G. and Janz D. 1991 Localization of idiopathic generalized epilepsy on chromosome 6p in families of juvenile myoclonic epilepsy patients.Neurology 41, 1651–1655.
Elmslie F. V., Rees M., Williamson M. P., Kerr M., Kjeldsen M. J., Pang K. A.et al. 1997 Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q.Hum. Mol. Genet. 6, 1329–1334.
Greenberg D. A. and Delgado-Escueta A. V. 1993 The chromosome 6p epilepsy locus: exploring mode of inheritance and heterogeneity through linkage analysis.Epilepsia 34 (suppl. 3), S12-S18.
Greenberg D. A., Delgado-Escueta A. V., Widelitz H., Sparkes R. S., Treiman L., Maldonado H. M.et al. 1988 Juvenile myoclonic epilepsy (JME) may be linked to the BF and HLA loci on human chromosome 6.Am. J. Med. Genet. 31, 185–192.
Greenberg D. A., Durner M., Keddache M., Shinnar S., Resor S. R., Moshe S. L.et al. 2000 Reproducibility and complications in gene searches: linkage on chromosome 6, heterogeneity, association, and maternal inheritance in juvenile myoclonic epilepsy.Am. J. Med. Genet. 66, 508–516.
Janz D. and Durner M. 1997 Juvenile myoclonic epilepsy. InEpilepsy: a comprehensive textbook (ed. J. Engel Jr and T. A. Pedley), pp. 2389–2400. Lippincott-Raven, Philadelphia.
Janz D., Durner M., Beck-Mannagetta G. and Pantazis G. 1989 Family studies on the genetics of juvenile myoclonic epilepsy (epilepsy with impulsive petit mal). InGenetics of the epilepsies (ed. G. Beck-Mannagetta, V. E. Anderson, H. Doose and D. Janz), pp. 43–52. Springer, Berlin.
Liu A. W., Delgado-Escueta A. V., Serratosa J. M., Alonso M. E., Medina M. T., Gee M. N.et al. 1995 Juvenile myoclonic epilepsy locus in the chromosome 6p21.2-p11: linkage to convulsions and electroencephalography trait.Am. J. Hum. Genet. 57, 368–381.
Liu A. W., Delgado-Escueta A. V., Gee M. N., Serratosa J. M., Zhang Q. W., Alonso M. E.et al. 1996 Juvenile myoclonic epilepsy in chromosome 6p12-p11: locus heterogeneity and recombinations.Am. J. Med. Genet. 63, 438–446.
Sambrook J. and Russell D. W. 2001Molecular cloning: a laboratory manual, 3rd edition. Cold Spring Harbor Laboratory Press, Cold Spring Harbor.
Sander T., Bockenkamp B., Hildmann T., Blasczyk R., Kretz R., Wienker T. F.et al. 1997 Refined mapping of the epilepsy susceptibility locusEJM1 on chromosome 6.Neurology 49, 842–847.
Schwartzkroin P. A. and Prince D. A. 1980 Changes in excitatory and inhibitory synaptic potentials leading to epileptogenic activity.Brain Res. 183, 61–76.
Steinlein O. K., Neubauer B. A., Sander T., Song L., Stoodt J. and Mount D. B. 2001 Mutation analysis of the potassium chloride cotransporter KCC3 (SLC12A6) in rolandic and idiopathic generalized epilepsy.Epilepsy Res. 44, 191–195.
Suzuki T., Morita R., Sugimoto Y., Sugawara T., Dong-Sheng Bai, Alonso M. E.et al. 2002 Identification and mutational analysis of candidate genes for juvenile myoclonic epilepsy on 6p11-p12: LRRC1, GCLC, KIAA0057 and CLIC5.Epilepsy Res. 50, 265–275.
Taske N. L., Williamson M. P., Makoff A., Bate L., Curtis D., Kerr M.et al. 2002 Evaluation of the positional candidate geneCHRNA7 at the juvenile myoclonic epilepsy locus (EJM2) on chromosome 15q13-14.Epilepsy Res. 49, 157–172.
Traub R. D. and Wong R. K. S. 1982 Cellular mechanism of neuronal synchronization in epilepsy.Science 216, 745–747.
Weissbecker K. A., Durner M., Janz D., Scaramelli A., Sparkes R. S. and Spence M. A. 1991 Confirmation of linkage between juvenile myoclonic epilepsy locus and the HLA region of chromosome 6.Am. J. Med. Genet. 38, 32–36.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kapoor, A., Vijai, J., Ravishankar, H.M. et al. Absence ofGABRA1 Ala322Asp mutation in juvenile myoclonic epilepsy families from India. J Genet 82, 17–21 (2003). https://doi.org/10.1007/BF02715876
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02715876