title: Genetic analysis of tuberous-sclerosis genes 1 and 2 in nonlesional focal epilepsy.
abstract: Germline mutations of TSC1 (harmartin) and TSC2 (tuberin) are known to cause tuberous sclerosis (TSC), an autosomal dominant disorder with severe neurological and systemic manifestations. In addition, increasing data indicate aberrant patterns of allelic variants in patients with lesion-associated epilepsy, but absence of other stigmata of TSC. Animal models of TSC suggested that mutations in the TSC2 gene, even in absence of manifest neuropathological changes, induce aberrant neuronal activity. On this basis, we have carried out a mutational analysis of TSC1 and TSC2 in patients with pharmarcoresistant focal epilepsy without evidence of epileptogenic lesions on neuroradiological and histopathological examination (n=10). SSCP analysis revealed an allelic variant of TSC2 to be significantly increased (exon 41: 50.0% vs controls 14%, P=0.0132), which previously was reported to be increased in gangliogliomas and mineralized focal cortical dysplasia as well. Our data suggest allelic imbalances of TSC2 in nonlesional focal epileptic tissue.
authors.affiliation: Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Schönberger
authors.forename: Eva
authors.initials: E
authors.lastname: Gembe
authors.forename: Alexander
authors.initials: A
authors.lastname: Grote
authors.forename: Juri-A
authors.initials: JA
authors.lastname: Witt
authors.forename: Christian E
authors.initials: CE
authors.lastname: Elger
authors.forename: Christian G
authors.initials: CG
authors.lastname: Bien
authors.forename: Horst
authors.initials: H
authors.lastname: Urbach
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Becker
authors.forename: Pitt
authors.initials: P
authors.lastname: Niehusmann
mesh_terms: D000328:Adult; D002648:Child; D004828:Epilepsies, Partial / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D018807:Polymorphism, Single-Stranded Conformational / Q000235:genetics*; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins