SUGGESTION OF A MAJOR GENE FOR FAMILIAL FEBRILE CONVULSIONS MAPPING TO 8Q13-21

Febrile convulsions affect 2 to 5% of all children under the age of 5 years. These convulsions probably have a variety of causes, but a gene tic component has long been recognised. A large and remarkable family is described in which febrile convulsions appear to result from autoso mal dominant inheritance at a single major locus. A gene for febrile c onvulsions was excluded from regions of previously mapped epilepsy gen es and extension of exclusion mapping, using microsatellite markers, t o the entire genome implied that a locus on chromosome 8q13-21 may be involved. Linkage analysis of markers on chromosome 8 gave a multipoin t lod score of 3.40, maximised over different values of penetrance and phenocopy rate, for linkage between the gene for febrile convulsions and the region flanked by markers D8S553 and D8S279. This lod score wa s calculated assuming the disease has a penetrance of 60% and a phenoc opy rate of 3%. Although there was no indication of linkage other than to markers on chromosome 8, linkage remains suggestive rather than si gnificant because of the maximisation procedure applied. The support f or linkage involving a major gene, as opposed to an alternative hypoth esis of a complex inheritance pattern, relied upon the assumption of l ow penetrance.