Description
One of the most intriguing findings of studies on the genetics of seizure disorders is the repeated observation of a maternal effect. In the first part of this work, the possibility that this effect results from a mutation in a mitochondrial (maternally inherited) gene is investigated. A rapid screening method for studying mitochondrial protein variation was developed. Two electrophoretic assays for mitochondrial protein variation were employed which permitted resolution of 17 or 18 mitochondrially encoded peptides. Using these gel systems the mitochondrial proteins of 91 individuals were screened and 4 polymorphic proteins identified. Three nuclear families were found to be informative for one of these polymorphisms (ME-8) and it was demonstrated that this protein is maternally inherited. The mitochondrial proteins of the members of nine families with a pattern of inheritance of seizures consistent with maternal inheritance were studied. No mitochondrial protein variants were found to be associated with seizures in any of these families. In the second part of this work, family histories of 143 probands with idiopathic seizures were studied to investigate the genetics of seizure disorders in this sample and determine whether or not a maternal effect was present. In this sample, 83/143 (58%) had sorre family history of seizures. Probands with any family history of seizures had a significantly younger age at onset than probands with no family history of seizures and probands with a maternal and a paternal family history of seizures had a younger age at onset of seizures than probands with any other type of family history. Of the 83 probands who reported having a family history of seizures, 43 were personally interviewed. Among this group, no maternal effect was observed. Among the entire group of probands with a family history (interviewed and not interviewed) there was an excess of probands who reported having a family history of seizures. This was found to result from the fact that among probands whose families were not interviewed, there were many families from which the father was absent, suggesting that the "maternal excess" of seizures results from a maternal reporting bias.
