title: A novel GEFS+ locus on 12p13.33 in a large Roma family.
abstract: We report a clinical and genetic follow-up study of a large consanguineous family from an endogamous Roma/Gypsy sub-isolate, where previous analyses have been inconclusive. Detailed clinical information was collected through extensive field work, repeat interviews and electrophysiological and neuroimaging investigations on 18 affected subjects. The phenotype is compatible with GEFS+, with some unusual features, e.g. GTCS persisting into late adult life and high frequency of focal epilepsy. Updated genealogical information, a dense SNP genome scan and linkage analysis identified a novel GEFS+ locus on 12p13.33, where 13 affected individuals from two branches of the kindred shared an identical haplotype. This haplotype was not found in the 3rd branch or in the remaining 21 Roma epilepsy families in our collection. Genetic heterogeneity and evidence of bilineality were found despite the inbreeding and endogamous nature of the family and population of origin. These data add to the growing evidence of lack of founder effect and significant genetic heterogeneity in epilepsy in the Roma/Gypsy population. Sequencing of the coding regions of three genes linked to neurotransmitter transport and release, SLC6A12, SLC6A13 and ERC1, on 12p did not identify a causative mutation.
authors.affiliation: Centre for Medical Research/Western Australian Institute for Medical Research, The University of Western Australia, Perth, Australia. bmorar@waimr.uwa.edu.au
authors.forename: Bharti
authors.initials: B
authors.lastname: Morar
authors.forename: Sashka
authors.initials: S
authors.lastname: Zhelyazkova
authors.forename: Dimitar N
authors.initials: DN
authors.lastname: Azmanov
authors.forename: Melania
authors.initials: M
authors.lastname: Radionova
authors.forename: Dora
authors.initials: D
authors.lastname: Angelicheva
authors.forename: Velina
authors.initials: V
authors.lastname: Guergueltcheva
authors.forename: Radka
authors.initials: R
authors.lastname: Kaneva
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: Ivailo
authors.initials: I
authors.lastname: Tournev
authors.forename: Luba
authors.initials: L
authors.lastname: Kalaydjieva
authors.forename: Josemir W
authors.initials: JW
authors.lastname: Sander
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics; D002881:Chromosomes, Human, Pair 12; D003241:Consanguinity; D004829:Epilepsy, Generalized / Q000235:genetics*; D005192:Family Health; D005260:Female; D018703:Founder Effect; D050485:GABA Plasma Membrane Transport Proteins / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D006178:Romani People / Q000235:genetics*; D003294:Seizures, Febrile / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C468925:ERC1 protein, human; D050485:GABA Plasma Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493418:SLC6A13 protein, human; C072207:betaine plasma membrane transport proteins