The first two authors contributed equally to this work.
Evidence for digenic inheritance in a family with both febrile convulsions and temporal lobe epilepsy implicating chromosomes 18qter and 1q25-q31
Article first published online: 2 APR 2001
Copyright © 2001 Wiley-Liss, Inc.
Annals of Neurology
Volume 49, Issue 6, pages 786–792, June 2001
How to Cite
Baulac, S., Picard, F., Herman, A., Feingold, J., Genin, E., Hirsch, E., Prud'Homme, J.-F., Baulac, M., Brice, A. and LeGuern, E. (2001), Evidence for digenic inheritance in a family with both febrile convulsions and temporal lobe epilepsy implicating chromosomes 18qter and 1q25-q31. Ann Neurol., 49: 786–792. doi: 10.1002/ana.1014
- Issue published online: 5 JUN 2001
- Article first published online: 2 APR 2001
- Manuscript Accepted: 24 JAN 2001
- Manuscript Revised: 27 NOV 2000
- Manuscript Received: 24 JUL 2000
- Association pour le Développement de la Recherche sur les Maladies Génétiques Neurologiques et Psychiatriques (ADRMGNP)
- Association Française contre les Myopathies (AFM)
- PHRC Strasbourg 1996. Grant Number: UF 9617
- Généthon, Paris, France
- ARGE (Association de Recherche sur la Génétique des Epilepsies)
We report a clinical and genetic study of a French family among whom febrile convulsions (FC) are associated with subsequent temporal lobe epilepsy (TLE) in the same individual, without magnetic resonance imaging-identifiable hippocampal abnormalities. Linkage analyses excluded the loci FEB1 and FEB2, previously implicated in FC; the GEFS+1 locus responsible for generalized epilepsy with febrile seizures plus; and the locus implicated in lateral temporal lobe epilepsy. After scanning the entire genome, significant lod scores (>3) for markers on 18qter and suggestive lod scores (>2) for markers on 1q25-q31 were obtained. An analysis of the haplotypes at these two loci supported the hypothesis that two genes segregated with the phenotype. All patients shared common haplotypes for both 1q25-q31 and 18qter chromosomes. All but one unaffected at-risk individuals carried only one, or none, of the disease haplotypes. Under the assumption of digenic inheritance, haplotype reconstruction defined a 26 cM interval on chromosome 1 and a 10 cM interval on chromosome 18. This family suggests that the association between FC and TLE may be observed in the absence of hippocampal structural abnormalities and that they may have, in some cases, a common genetic basis.