Abstracts

Familial temporal lobe epilepsy with auditory auras (FTLEAA) has been recognized as a seizure disorder in which simple partial seizures present with characteristic auditory features. A locus on chromosome 10q has been linked to FTLEAA, and more recently mutations in the leucine rich gliome inactivate 1 gene [italic]LGI1 [/italic]have been found in affected individuals belonging to different FTLEAA families. The objectives this study is to investigate the presence of MRI abnormalities in patients and asymptomatic individuals with [italic]LGI 1[/italic] mutations belonging to a large family segregating FTLEAA.
We studied 21 individuals, including 16 patients and 5 asymptomatic relatives. High resolution MRI was performed for evaluation of temporal lobe structures. For mutation analysis, we screened the entire coding region of the [italic]LGI1[/italic] gene by PCR, using primers that flanked intron-exon junctions. Nucleotide sequences for three affected members of this family and three individual of a control group were analyzed using dye-terminators chemistry for MegaBACE 1000[reg]. After sequencing characterization of the mutations a BstN I restriction enzyme analysis was performed to evaluated all individuals recruited for the study, including 12 unrelated normal controls
Mean age at seizure onset was 19 years. MRI abnormalities were observed in 8/16 (50%) patients. These were subtle dysmorphic features, including enlargement (increased amount of white matter) and absence/distortion of the major sulci and gyri of the baso-lateral temporal lobe. Nucleotide sequencing and restriction enzyme analysis revelead a VIIIS7(-2)A-G splice site mutation in all 16 symptomatic individuals and in 4 asymptomatic first degree relatives, all of them (n=4) with no MRI abnormalities. No mutations were found in normal control subjects.
VIIIS7(-2)A-G mutation was present in both symptomatic and asymptomatic relatives. This fact could be due the age-dependent penetrance of FTLEAA, since our asymptomatic individuals with [italic]LGI1[/italic] mutation have less than 18 years of age. The structural MRI abnormalities detected in this study were subtle and not present in all individuals with clinical symptoms and with the [italic]LGI1[/italic] mutation. The relevance of these MRI findings for the cause-relationship between seizures and [italic]LGI1[/italic] mutation is still uncertain. However, they may represent the [ldquo]tip of the iceberg[rdquo] of a yet undetermined malformation of white matter and cortical development. Further studies with other neuroimaging modalities may help to clarify the role of [italic]LGI1[/italic] mutations in the development of seizures in FTLEAA.
[Supported by: FAPESP and CAPES.]