Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014547 (focal epilepsy)
 1,627 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gangliogliomas and focal cortical dysplasias (FCDs) constitute glioneuronal lesions, which are frequently encountered in biopsy specimens of patients with pharmacoresistant focal epilepsy and relate to impaired differentiation and migration of neural precursors. However, their molecular pathogenesis and relationship are still largely enigmatic. Recent data suggest several components of the insulin-pathway, including TSC1 and TSC2 mutated in tuberous sclerosis complex (TSC), to be altered in gangliogliomas and FCD with Taylor type balloon cells (FCD(IIb)). The proteins tuberin (TSC2) and hamartin (TSC1) constitute a tumour suppressor mechanism involved in cell-cycle control. Hamartin and/or tuberin were reported to colocalize and/or interact with CDK1, cyclinB1 and cyclinA2 that are critically involved in cell-size and cell-growth control. Here, we have carried out mutational and expression analyses of CDK1, cyclinB1 and cyclinA2 in gangliogliomas and FCD(IIb). Mutational screening was performed by single-strand conformation polymorphism analysis in gangliogliomas (n = 20), FCD(IIb) (n = 35) and controls. CyclinB1 revealed a polymorphism (G to A, cDNA Position 966, GenBank: NM_031966) in exon 7 with similar frequencies in FCD(IIb), gangliogliomas and control specimens (FCD n = 9/35; gangliogliomas n = 5/20; control n = 20/100). We used real-time reverse transcription polymerase chain reaction to determine expression levels of CDK1, cyclinB1 and cyclinA2 in 10 FCD(IIb) and nine gangliogliomas compared with unaffected adjacent control tissue of the same patients. We observed significantly lower expression of CDK1 and cyclinA2 in FCD(IIb) vs. controls whereas no significant expression differences were present for CDK1, cyclinB1 and cyclinA2 in gangliogliomas. Our data strongly argue against mutational events of CDK1, cyclinB1 and cyclinA2 to play a role in gangliogliomas or FCD(IIb). However, a potential functional significance of lower expression for the cell-size and cell-cycle regulators CDK1 and cyclinA2 in FCD(IIb) composed of large dysplastic neurones and balloon cells needs to be further resolved.
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PMID:Mutational and expression analysis of CDK1, cyclinA2 and cyclinB1 in epilepsy-associated glioneuronal lesions. 1735 56

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.
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PMID:Genetic analysis of tuberous-sclerosis genes 1 and 2 in nonlesional focal epilepsy. 2155 52