Partial epilepsy syndrome in a Gypsy family linked to 5q31.3-q32

Purpose: The restricted genetic diversity andhomogeneous molecular basis of Mendelian disordersin isolated founder populations have rarelybeen explored in epilepsy research.Our long-termgoal is to explore the genetic basis of epilepsies inone such population, the Gypsies. The aim of thisreport is the clinical and genetic characterizationof a Gypsy family with a partial epilepsy syndrome.Methods: Clinical information was collected usingsemistructured interviews with affected subjectsand informants. At least one interictal electroencephalography(EEG) recording was performedfor each patient and previous data obtained fromrecords. Neuroimaging included structural magneticresonance imaging (MRI). Linkage and haplotypeanalysis was performed using the Illumina IVbLinkage Panel, supplemented with highly informativemicrosatellites in linked regions and AffymetrixSNP 5.0 array data.Results: We observed an early-onset partial epilepsysyndrome with seizure semiology stronglysuggestive of temporal lobe epilepsy (TLE), withmild intellectual deficit co-occurring in a largeproportion of the patients. Psychiatric morbiditywas common in the extended pedigree but didnot cosegregate with epilepsy. Linkage analysisdefinitively excluded previously reported loci, andidentified a novel locus on 5q31.3-q32 with an logarithmof the odds (LOD) score of 3 correspondingto the expected maximum in this family.Discussion: The syndrome can be classified asfamilial temporal lobe epilepsy (FTLE) or possiblya new syndrome with mild intellectual deficit. Thelinked 5q region does not contain any ion channel–encoding genes and is thus likely to contribute newknowledge about epilepsy pathogenesis. Identificationof the mutation in this family and in additionalpatients will define the full phenotypicspectrum.