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Evidence for digenic inheritance in a family with both febrile convulsions and temporal lobe epilepsy implicating chromosomes 18qter and 1q25‐q31
Author(s) -
Baulac Stéphanie,
Picard Fabienne,
Herman Alexandra,
Feingold Josué,
Genin Emmanuelle,
Hirsch Edouard,
Prud'Homme JeanFrançois,
Baulac Michel,
Brice Alexis,
LeGuern Eric
Publication year - 2001
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.1014
Subject(s) - temporal lobe , epilepsy , haplotype , locus (genetics) , genetics , genetic linkage , biology , neuroscience , gene , allele
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.