Partial epilepsy syndrome in a Gypsy family linked to 5q31.3-q32.
OBJECTIVE
The restricted genetic diversity and homogeneous molecular basis of Mendelian disorders in isolated founder populations have rarely been explored in epilepsy research. Our long-term goal is to explore the genetic basis of epilepsies in one such population, the Gypsies. The aim of this report is the clinical and genetic characterization of a Gypsy family with a partial epilepsy syndrome.


METHODS
Clinical information was collected using semistructured interviews with affected subjects and informants. At least one interictal electroencephalography (EEG) recording was performed for each patient and previous data obtained from records. Neuroimaging included structural magnetic resonance imaging (MRI). Linkage and haplotype analysis was performed using the Illumina IVb Linkage Panel, supplemented with highly informative microsatellites in linked regions and Affymetrix SNP 5.0 array data.


RESULTS
We observed an early-onset partial epilepsy syndrome with seizure semiology strongly suggestive of temporal lobe epilepsy (TLE), with mild intellectual deficit co-occurring in a large proportion of the patients. Psychiatric morbidity was common in the extended pedigree but did not cosegregate with epilepsy. Linkage analysis definitively excluded previously reported loci, and identified a novel locus on 5q31.3-q32 with an logarithm of the odds (LOD) score of 3 corresponding to the expected maximum in this family.


CONCLUSIONS
The syndrome can be classified as familial temporal lobe epilepsy (FTLE) or possibly a new syndrome with mild intellectual deficit. The linked 5q region does not contain any ion channel-encoding genes and is thus likely to contribute new knowledge about epilepsy pathogenesis. Identification of the mutation in this family and in additional patients will define the full phenotypic spectrum.
Angelicheva
Dora
D
Laboratory for Molecular Genetics, Centre for Medical Research and Western Australian Institute for Medical Research, The University of Western Australia, Perth, Australia.
Tournev
Ivailo
I
Guergueltcheva
Velina
V
Mihaylova
Violeta
V
Azmanov
Dimitar N
DN
Morar
Bharti
B
Radionova
Melania
M
Smith
Shelagh J
SJ
Zlatareva
Dora
D
Stevens
John M
JM
Kaneva
Radka
R
Bojinova
Veneta
V
Carter
Kim
K
Brown
Matthew
M
Jablensky
Assen
A
Kalaydjieva
Luba
L
Sander
Josemir W
JW
D000293:Adolescent; D000328:Adult; D002648:Child; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D004569:Electroencephalography; D004828:Epilepsies, Partial / Q000453:epidemiology / Q000235:genetics*; D004833:Epilepsy, Temporal Lobe / Q000453:epidemiology / Q000235:genetics; D005260:Female; D018703:Founder Effect; D008040:Genetic Linkage / Q000235:genetics; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D006178:Romani People / Q000235:genetics* / Q000706:statistics & numerical data; D013577:Syndrome