Abstracts

We previously reported that mutations in LGI1 are present in 50% of families containing [ge]2 individuals with idiopathic focal epilepsy with ictal auditory symptoms. However, mutations have not been found either in familial temporal lobe epilepsies without auditory symptoms, or nonfamilial epilepsies with auditory symptoms. Here we investigated mutation frequency in a different group: familial epilepsies in which one subject had ictal auditory symptoms. The results can be used to refine prediction of which families are likely to carry a mutation in this gene. The study included 28 families each of which contained one subject with ictal auditory symptoms. Two neurologists classified partial seizure semiology in each affected individual in the families. To detect sequence variants in LGI1, the gene[apos]s eight coding exons were sequenced in DNA extracted from blood or EBV-transformed lymphoblastoid cell lines. For analysis of clinical and molecular data, the 28 newly studied families were combined with 14 previously reported families containing [ge]2 subjects with auditory symptoms. The 28 families contained a total of 95 subjects with idiopathic epilepsy (average 3.4 per family), of whom 58 had focal epilepsy, and 28 (1 subject per family) had auditory symptoms. None of these families had a mutation in LGI1. Excluding the original linkage family used to define this syndrome, we have analyzed 42 families for mutations in LGI1 (28 reported here and 14 reported previously), seven of which have had mutations. To detect family characteristics that might predict which have a mutation, we classified each family by the percent of affected subjects whose epilepsy was focal, the percent of subjects with focal epilepsy who had auditory symptoms, and the percent of subjects with focal epilepsy who had autonomic symptoms. Families with mutations did not differ from those without mutations in the total number of individuals with idiopathic epilepsy (4.3 vs. 3.6), or the percent whose epilepsy was focal (average per family: 80% vs. 73%). However, among subjects with focal epilepsy, the percent with ictal auditory symptoms was greater in families with mutations than in those without (average per family: 98% vs. 59%, p=0.001), and the percent with autonomic symptoms was lower in families with mutations than in those without (average per family 19% vs. 50%, p=0.035). The families most likely to have mutations in LGI1 are those containing multiple subjects with idiopathic focal epilepsy, a majority of whom have auditory symptoms, and a minority of whom have autonomic symptoms. This symptom constellation reflects a high probability of a lateral temporal localization of the epileptogenic zone. (Supported by NIH R01 NS36319)