Abstract
There is strong evidence for a genetic contribution to epilepsy, but it is commonly assumed that this genetic contribution is limited to ‘generalized’ epilepsies, and that most forms of ‘partial’ epilepsy are nongenetic. In a linkage analysis of a single family containing 11 affected individuals, we obtained strong evidence for localization of a gene for partial epilepsy. This susceptibility gene maps to chromosome 10q, with a maximum two–point lod score for D10S192 of 3.99 at θ=0.0. All affected individuals share a single haplotype for seven tightly linked contiguous markers; the maximum lod score for this haplotype is 4.83 at θ=0.0. Key recombinants place the susceptibility locus within a 10 centimorgan interval.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Hauser, W.A., Annegers, J.F. & Kurland, L.T. Prevalence of epilepsy in Rochester, Minnesota, 1940–1980. Epilepsia 31, 429–445 (1991).
Hauser, W.A., Annegers, J.F. & Kurland, L.T. Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935–1984. Epilepsia 34, 453–468 (1993).
Leppert, M. et al. Benign familial neonatal convulsions linked to genetic markers on chromosome 20. Nature 337, 647–648 (1989).
Lewis, T.B., Leach, R.J., Ward, K., O'Connell, P. & Ryan, S.G. Genetic heterogeneity in benign familial neonatal convulsions: identification of a new locus on chromosome 8q. Am. J. hum. Genet. 53, 670–675 (1993).
Steinlein, O. et al. Refinement of the localization of the gene for neuronal nicotinic acetylcholine receptor α4 subunit (CHRNA4) to human chromosome 20q13.2–q13.3. Genomics 22, 493–495 (1994).
Lehesjoki, A.-E. et al. Localization of a gene for progressive myoclonus epilepsy to chromosome 21q22. Proc. natn. Acad. Sci. U.S.A. 88, 3696–3699 (1991).
Greenberg, D.A. et al. Juvenile myoclonic epilepsy may be linked to the BF and HLA loci on human chromosome 6. Am. J. Med. Genet. 31, 185–192 (1988).
Weissbecker, K.A., Durner, M., Janz, D., Scaramelli, A., Sparkes, R.S. & Spence, M.A. Confirmation of linkage between juvenile myoclonic epilepsy locus and the HLA region of chromosome 6. Am. J. Med. Genet. 38, 32–86 (1991).
Durner, M., Sander, T., Greenberg, D.A., Johnson, K., Beck-Mannagetta, G. & Janz, D. Localization of idiopathic generalized epilepsy on chromosome 6p in families ascertained through juvenile myoclonic epilepsy patients. Neurology 41, 1651–1655 (1991).
Whitehouse, W.P. et al. 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. 53, 652–662 (1993).
Commission on Classification and Terminololgy of the International League Against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 22, 489–501 (1981).
Commission on Classification and Terminology of the International League Against Epilepsy. A revised proposal for the classification of epilepsy and epileptic syndromes. Epilepsia 30, 268–278 (1989).
Ottman, R. Genetics of the partial epilepsies: a review. Epilepsia 30, 107–111 (1989).
Ottman, R., Annegers, J.F., Hauser, W.A. & Kurland, L.T. Seizure risk in offspring of parents with generalized vs. partial epilepsy. Epilepsia 30, 157–161 (1989).
Heijbel, J., Blom, S. & Rasmuson, M. Benign epilepsy of childhood with centrotemporal EEG foci: a genetic study. Epilepsia 16, 285–93 (1975).
Scheffer, I.E. et al. Autosomal dominant frontal epilepsy misdiagnosed as sleep disorder. Lancet 343, 515–517 (1994).
Ottman, R. & Susser, M. Data collection strategies in genetic epidemiology: the Epilepsy Family Study of Columbia University. J. din. Epidemiol. 45, 721–727 (1992).
Lathrop, G.M. & Lalouel, J.M. Easy calculations of lod scores and genetic risks on small computers. Am. J. hum. Genet. 36, 460–465 (1984).
Lathrop, G.M. & Lalouel, J.M. Efficient computations in multilocus linkage analysis. Am. J. hum. Genet. 42, 498–505 (1988).
Cottingham, R.W., Jr Idury, R.M. & Schaffer, A.A. Faster sequential genetic linkage computations. Am. J. hum. Genet. 53, 252–263 (1993).
Ottman, R. & Sherman, S. Genetic analysis of epilepsy in families ascertained from voluntary organizations [abstract]. Epilepsia 31, 611 (1990).
Gyapay, G. et al. The 1993–94 Genethon human genetic linkage map. Nature Genet. 7, 246–339 (1994).
Ottman, R., Lee, J.H., Hauser, W.A. & Risch, N. Birth cohort and familial risk of epilepsy: the effect of diminished recall in studies of lifetime prevalence. Am. J. Epidemiol. (in the press).
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. 44, 388–396 (1989).
Tautz, D. Hypervariability of simple sequences as a general source for polymorphic DNA markers. Nucl. Acids Res. 17, 6463–6471 (1989).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ottman, R., Risch, N., Hauser, W. et al. Localization of a gene for partial epilepsy to chromosome 10q. Nat Genet 10, 56–60 (1995). https://doi.org/10.1038/ng0595-56
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ng0595-56
This article is cited by
-
The LGI1 protein: molecular structure, physiological functions and disruption-related seizures
Cellular and Molecular Life Sciences (2022)
-
Genetic Epilepsy Syndromes Without Structural Brain Abnormalities: Clinical Features and Experimental Models
Neurotherapeutics (2014)
-
Mutations of DEPDC5 cause autosomal dominant focal epilepsies
Nature Genetics (2013)
-
Genetics of Epilepsy and Relevance to Current Practice
Current Neurology and Neuroscience Reports (2012)
-
The temporal and spatial expression pattern of the LGI1 epilepsy predisposition gene during mouse embryonic cranial development
BMC Neuroscience (2011)