Abstracts

Rationale: We identified a family with autosomal dominant lateral temporal lobe epilepsy (ADLTLE) as part of the Wales Epilepsy Research Network (WERN) genetics of familial epilepsy programme. Given that LGI1 mutations account for around 50% of families with ADLTLE, we screened family members for LGI1 variants. Methods: Detailed clinical information was obtained through interview and review of medical notes. Sanger sequencing was performed for all exonic regions of LGI1. In-silico analysis tools were used to assess the potential affect of all novel variants identified and a protein modelling pipeline was used to assess the potential structural effects of the variant. Results: Clinical features : The proband is a 48-year-old woman who has had epilepsy since the age of 13. Her seizures consist of a unilateral ‘buzzing' sensation which occasionally progresses to a unilateral limb numbness and then secondarily generalised seizures. Some noises including telephones and alarms can provoke seizures. Her mother developed epilepsy at the age of 17 with identical clinical semiology. The proband's daughters aged 18 and 15 have never had epileptic seizures. Molecular genetics : We identified a novel heterozygous missense LGI1 variant in the proband and her mother but not in other family members. This variant is close to the splice site region of LGI1 exon 4 and is predicted to be deleterious by variant prediction software. Protein modelling suggests that the mutation causes conformational structural changes to the epitempin region of the LGI1 protein. We are undertaking further work in order to characterise the functional consequences of the variant. Conclusions: We present a family with ADLTLE caused by a novel variant in LGI1. This variant is predicted to be deleterious, alters protein function and adds additional evidence for the role of LGI1 in ADTLE.