National Cancer Institute®
Last Modified: July 1, 2002
UI - 12015165
AU - Yamamoto T; Pipo JR; Feng JH; Takeda H; Nanba E; Ninomiya H; Ohno K
TI - Novel TSC1 and TSC2 mutations in Japanese patients with tuberous sclerosis complex.
SO - Brain Dev 2002 Jun;24(4):227-30
AD - Gene Research Center, Tottori University, Yonago 683-8503, Japan. email@example.com
Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome characterized by development of unusual tumor-like growths. Involvement of the brain is associated with the most problematic clinical manifestations of TSC, including intellectual retardation, epilepsy and abnormal behaviors. Until now, over 300 mutations of TSC1 and TSC2 were reported. Here, we report one novel mutation of TSC1 (Q897X) and five novel mutations of TSC2 (c.336+1 G>A, L345R, E700K, R905G, K914K) identified in Japanese patients with TSC. We also identified three new polymorphisms in TSC2 (N331N, A431A, S802G). The TSC1 mutation was predicted to cause a nonsense substitution whereas all of the five TSC2 mutations were predicted to cause either a splicing error or a missense substitution. In accordance with previous findings, the patients with TSC1 mutations had milder clinical manifestations than those with TSC2 mutations.
UI - 12112044
AU - Becker AJ; Urbach H; Scheffler B; Baden T; Normann S; Lahl R; Pannek HW;
TI - Tuxhorn I; Elger CE; Schramm J; Wiestler OD; Blumcke I Focal cortical dysplasia of Taylor's balloon cell type: mutational analysis of the TSC1 gene indicates a pathogenic relationship to tuberous sclerosis.
SO - Ann Neurol 2002 Jul;52(1):29-37
AD - Department of Neuropathology, FE Neuroradiology, University of Bonn Medical Center, Bonn, Germany.
Focal cortical dysplasia (FCD) is characterized by a localized malformation of the neocortex and underlying white matter. Balloon cells, similar to those observed in tuberous sclerosis, are present in many cases (FCD(bc)). In these patients, a hyperintense funnel-shaped subcortical lesion tapering toward the lateral ventricle was the characteristic finding on fluid-attenuated inversion recovery magnetic resonance imaging scans. Surgical lesionectomy results in complete seizure relief. Although the pathogenesis of FCD(bc) remains uncertain, histopathological similarities indicate that FCD(bc) may be related pathogenetically to tuberous sclerosis. Here, we studied alterations of the TSC1 and TSC2 genes in a cohort of patients with chronic, focal epilepsy and histologically documented FCD(bc) (n = 48). DNA was obtained after microdissection and laser-assisted isolation of balloon cells, dysplastic neurons, and nonlesional cells from adjacent normal brain tissue. Sequence alterations resulting in amino acid exchange of the TSC1 gene product affecting exons 5 and 17 and silent base exchanges in exons 14 and 22 were increased in patients with FCD(bc) compared with 200 control individuals (exon 5, 2.3% FCD(bc) vs 0% C; exon 17, 35% FCD(bc) vs 1.0% C; exon 14, 37.8% FCD(bc) vs 15% C; exon 22, 45% FCD(bc) vs 23.8% C). Sequence alterations could be detected in FCD(bc) and in adjacent normal cells. In 24 patients, DNA was suitable to study loss of heterozygosity at the TSC1 gene locus in microdissected FCD(bc) samples compared with control tissue. Eleven FCD(bc) cases exhibited loss of heterozygosity. In the TSC2 gene, only silent polymorphisms were detected at similar frequencies as in controls. Our findings indicate that FCD(bc) constitutes a clinicopathological entity with distinct neuroradiological, neuropathological, and molecular genetic features. These data also suggest a role of the TSC1 gene in the development of FCD(bc) and point toward a pathogenic relationship between FCD(bc) and the tuberous sclerosis complex.
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