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. 1998 Oct;63(4):1117–1129. doi: 10.1086/302066

Childhood absence epilepsy with tonic-clonic seizures and electroencephalogram 3-4-Hz spike and multispike-slow wave complexes: linkage to chromosome 8q24.

G C Fong 1, P U Shah 1, M N Gee 1, J M Serratosa 1, I P Castroviejo 1, S Khan 1, S H Ravat 1, J Mani 1, Y Huang 1, H Z Zhao 1, M T Medina 1, L J Treiman 1, G Pineda 1, A V Delgado-Escueta 1
PMCID: PMC1377498  PMID: 9758624

Abstract

Childhood absence epilepsy (CAE), a common form of idiopathic generalized epilepsy, accounts for 5%-15% of childhood epilepsies. To map the chromosomal locus of persisting CAE, we studied the clinical and electroencephalographic traits of 78 members of a five-generation family from Bombay, India. The model-free affected-pedigree member method was used during initial screening with chromosome 6p, 8q, and 1p microsatellites, and only individuals with absence seizures and/or electroencephalogram 3-4-Hz spike- and multispike-slow wave complexes were considered to be affected. Significant P values of .00000-.02 for several markers on 8q were obtained. Two-point linkage analysis, assuming autosomal dominant inheritance with 50% penetrance, yielded a maximum LOD score (Zmax) of 3.6 for D8S502. No other locus in the genome achieved a significant Zmax. For five smaller multiplex families, summed Zmax was 2.4 for D8S537 and 1.7 for D8S1761. Haplotypes composed of the same 8q24 microsatellites segregated with affected members of the large family from India and with all five smaller families. Recombinations positioned the CAE gene in a 3.2-cM interval.

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Selected References

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  1. Cavazzuti G. B. Epidemiology of different types of epilepsy in school age children of Modena, Italy. Epilepsia. 1980 Feb;21(1):57–62. doi: 10.1111/j.1528-1157.1980.tb04044.x. [DOI] [PubMed] [Google Scholar]
  2. Chandy K. G., Gutman G. A. Nomenclature for mammalian potassium channel genes. Trends Pharmacol Sci. 1993 Dec;14(12):434–434. doi: 10.1016/0165-6147(93)90181-i. [DOI] [PubMed] [Google Scholar]
  3. Chumakov I. M., Rigault P., Le Gall I., Bellanné-Chantelot C., Billault A., Guillou S., Soularue P., Guasconi G., Poullier E., Gros I. A YAC contig map of the human genome. Nature. 1995 Sep 28;377(6547 Suppl):175–297. doi: 10.1038/377175a0. [DOI] [PubMed] [Google Scholar]
  4. Dib C., Fauré S., Fizames C., Samson D., Drouot N., Vignal A., Millasseau P., Marc S., Hazan J., Seboun E. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152–154. doi: 10.1038/380152a0. [DOI] [PubMed] [Google Scholar]
  5. Durner M., Sander T., Greenberg D. A., Johnson K., Beck-Mannagetta G., Janz D. Localization of idiopathic generalized epilepsy on chromosome 6p in families of juvenile myoclonic epilepsy patients. Neurology. 1991 Oct;41(10):1651–1655. doi: 10.1212/wnl.41.10.1651. [DOI] [PubMed] [Google Scholar]
  6. Lander E., Kruglyak L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet. 1995 Nov;11(3):241–247. doi: 10.1038/ng1195-241. [DOI] [PubMed] [Google Scholar]
  7. Lewis T. B., Wood S., Michaelis E. K., DuPont B. R., Leach R. J. Localization of a gene for a glutamate binding subunit of a NMDA receptor (GRINA) to 8q24. Genomics. 1996 Feb 15;32(1):131–133. doi: 10.1006/geno.1996.0088. [DOI] [PubMed] [Google Scholar]
  8. Liu A. W., Delgado-Escueta A. V., Serratosa J. M., Alonso M. E., Medina M. T., Gee M. N., Cordova S., Zhao H. Z., Spellman J. M., Peek J. R. Juvenile myoclonic epilepsy locus in chromosome 6p21.2-p11: linkage to convulsions and electroencephalography trait. Am J Hum Genet. 1995 Aug;57(2):368–381. [PMC free article] [PubMed] [Google Scholar]
  9. METRAKOS K., METRAKOS J. D. Genetics of convulsive disorders. II. Genetic and electroencephalographic studies in centrencephalic epilepsy. Neurology. 1961 Jun;11:474–483. doi: 10.1212/wnl.11.6.474. [DOI] [PubMed] [Google Scholar]
  10. MORTON N. E. Sequential tests for the detection of linkage. Am J Hum Genet. 1955 Sep;7(3):277–318. [PMC free article] [PubMed] [Google Scholar]
  11. Ott J. Estimation of the recombination fraction in human pedigrees: efficient computation of the likelihood for human linkage studies. Am J Hum Genet. 1974 Sep;26(5):588–597. [PMC free article] [PubMed] [Google Scholar]
  12. Risch N. A note on multiple testing procedures in linkage analysis. Am J Hum Genet. 1991 Jun;48(6):1058–1064. [PMC free article] [PubMed] [Google Scholar]
  13. Serratosa J. M., Delgado-Escueta A. V., Medina M. T., Zhang Q., Iranmanesh R., Sparkes R. S. Clinical and genetic analysis of a large pedigree with juvenile myoclonic epilepsy. Ann Neurol. 1996 Feb;39(2):187–195. doi: 10.1002/ana.410390208. [DOI] [PubMed] [Google Scholar]
  14. Toth M., Grimsby J., Buzsaki G., Donovan G. P. Epileptic seizures caused by inactivation of a novel gene, jerky, related to centromere binding protein-B in transgenic mice. Nat Genet. 1995 Sep;11(1):71–75. doi: 10.1038/ng0995-71. [DOI] [PubMed] [Google Scholar]
  15. Weber J. L., May P. E. Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet. 1989 Mar;44(3):388–396. [PMC free article] [PubMed] [Google Scholar]
  16. Weeks D. E., Lange K. The affected-pedigree-member method of linkage analysis. Am J Hum Genet. 1988 Feb;42(2):315–326. [PMC free article] [PubMed] [Google Scholar]
  17. Whitehouse W. P., Rees M., Curtis D., Sundqvist A., Parker K., Chung E., Baralle D., Gardiner R. M. Linkage analysis of idiopathic generalized epilepsy (IGE) and marker loci on chromosome 6p in families of patients with juvenile myoclonic epilepsy: no evidence for an epilepsy locus in the HLA region. Am J Hum Genet. 1993 Sep;53(3):652–662. [PMC free article] [PubMed] [Google Scholar]
  18. Zara F., Bianchi A., Avanzini G., Di Donato S., Castellotti B., Patel P. I., Pandolfo M. Mapping of genes predisposing to idiopathic generalized epilepsy. Hum Mol Genet. 1995 Jul;4(7):1201–1207. doi: 10.1093/hmg/4.7.1201. [DOI] [PubMed] [Google Scholar]

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