Background We identified a family with autosomal dominant lateral temporal lobe epilepsy (ADLTLE). Given that LGI1 mutations account for around 50% of families with ADLTLE, we screened family members for LGI1 variants.
Method We sequenced all exonic regions of LGI1 and used in-silico analysis tools to assess the potential affect of the novel variant. We screened 106 control samples for the variant and assessed the structural effect of the variant using a protein modelling platform.
Results The proband's seizures consist of an unilateral ‘buzzing’ sensation which progresses to unilateral limb numbness and secondarily generalised seizures. Some noises can provoke seizures. Her mother also has epilepsy with identical seizure semiology. We identified a novel heterozygous missense LGI1 variant in the proband and her mother which was not present in other family members or control samples. This variant is close to the splice site region of LGI1 exon 4 and is predicted to be deleterious. Protein modelling suggests that the variant causes conformational structural changes.
Conclusion 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 ADLTLE.