Abstracts

A number of familial temporal lobe epilepsies (TLE) have been recently recognized. Mutations in LGI1 (leucine-rich, glioma-inactivated 1 gene) were found in a few families with the syndrome of autosomal dominant partial epilepsy with auditory features (ADPEAF). We aimed to determine the spectrum of TLE phenotypes with LGI1 mutations, to study the frequency of mutations in ADPEAF and to examine the role of LGI1 orthologs in ADPEAF without LGI1 mutations.
We performed a clinical and molecular analysis on 75 pedigrees comprising 54 with a variety of familial epilepsies associated with TLE and 21 sporadic TLE cases. All were studied for mutations in LGI1. ADPEAF families negative for LGI1 mutations were screened for mutations in LGI2, LGI3 and LGI4.
Four families had ADPEAF, 22 had mesial TLE, 11 had TLE with febrile seizures, 2 had TLE with developmental abnormalities, and 15 had various other TLE syndromes. LGI1 mutations were found in 2/4 ADPEAF families, but in none of the other 50 families nor in the 21 individuals with sporadic TLE. The mutations were novel missense mutations in exons 1 (c.124T-[gt]G; C42G) and 8 (c.1418C-[gt]T; S473L). No mutations in LGI2, LGI3 or LGI4 were found in the other two ADPEAF families
In TLE, mutations in LGI1 are specific for ADPEAF but do not occur in all families. Both mutations identified were missense, unlike previous reports where truncation mutations were usual. ADPEAF is genetically heterogeneous, but mutations in LGI2, LGI3 or LGI4 did not account for families without LGI1 mutations.
[Supported by: Bionomics Ltd]