Genotype/Phenotype Correlations in Tuberous Sclerosis Complex

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the development of widespread hamartomatous lesions in various organs including brain, skin, kidneys, heart and eyes. Central nervous system is almost invariably involved, with up to 85% of patients presenting with epilepsy, and at least half of patients presenting intellectual disability and/or other neuropsychiatric disorders including autism spectrum disorder. TSC is caused by the mutation in one of the two genes TSC1, at 9q34, and TSC2, at 16p13.3.
Source: Seminars in Pediatric Neurology - Category: Neurology Authors: Source Type: research

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AbstractTuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by epilepsy, intellectual disability, and benign tumors of the brain, heart, skin, and kidney. Animal models have contributed to our understanding of normal and abnormal human brain development, but the construction of models that accurately recapitulate a human pathology remains challenging. Recent advances in stem cell biology with the derivation of human-induced pluripotent stem cells (hiPSCs) from somatic cells from patients have opened new avenues to the study of TSC. This approach combined with gene-editing tools such as CRISPR/C...
Source: Molecular Autism - Category: Molecular Biology Source Type: research
ConclusionsDifferent types of glial cells have both cell autonomous effects and interactions with neurons and other cells that are involved in the pathophysiology of the neurological phenotype of TSC. Targeting glial-mediated mechanisms may represent a novel therapeutic approach for epilepsy and TAND in TSC patients.
Source: Journal of Neurodevelopmental Disorders - Category: Neurology Source Type: research
Tuberous sclerosis complex (TSC) is a neurogenetic disorder associated with epilepsy, intellectual disabilities, and autistic behaviors. These neurological symptoms result from synaptic dysregulations, which s...
Source: Molecular Brain - Category: Neuroscience Authors: Tags: Research Source Type: research
[Neuropsychiatric manifestations in Tuberous Sclerosis Complex (TSC): diagnostic guidelines, TAND concept and therapy with mTOR inhibitors]. Z Kinder Jugendpsychiatr Psychother. 2018 Aug 06;:1-14 Authors: Waltereit R, Feucht M, de Vries MC, Huemer J, Roessner V, de Vries PJ Abstract Neuropsychiatric manifestations in Tuberous Sclerosis Complex (TSC): diagnostic guidelines, TAND concept and therapy with mTOR inhibitors Abstract. Tuberous sclerosis complex (TSC), albeit a rare autosomal-dominant multisystem disease with an incidence of 1:6,000, is one of the most important monogenetic disorders in ...
Source: Zeitschrift fur Kinder- und Jugendpsychiatrie und Psychotherapie - Category: Child Development Tags: Z Kinder Jugendpsychiatr Psychother Source Type: research
We report the molecular diagnosis of TSC in individuals exhibiting extreme intra-familial variability, including the incidental diagnosis of asymptomatic family members. Exome sequencing was performed in three families, with probands referred for epilepsy, autism, and absent speech (Family 1); epileptic spasms (Family 2); and connective tissue disorders (Family 3.) Pathogenic variants inTSC1 orTSC2 were identified in nine individuals, including relatives with limited or no medical concerns at the time of testing. Of the nine individuals reported here, six had post-diagnosis examinations and three met clinical diagnostic cr...
Source: Neurogenetics - Category: Genetics & Stem Cells Source Type: research
Authors: Curatolo P, Moavero R, van Scheppingen J, Aronica E Abstract INTRODUCTION: The mammalian target of rapamycin (mTOR) pathway has emerged as a key player for proper neural network development, and it is involved in epileptogenesis triggered by both genetic or acquired factors. Areas covered. The robust mTOR signaling deregulation observed in a large spectrum of epileptogenic developmental pathologies, such as focal cortical dysplasias and tuberous sclerosis complex (TSC), has been linked to germline and somatic mutations in mTOR pathway regulatory genes, increasing the spectrum of "mTORopathies". The ...
Source: Expert Review of Neurotherapeutics - Category: Neurology Tags: Expert Rev Neurother Source Type: research
Publication date: 25 July 2017 Source:Cell Reports, Volume 20, Issue 4 Author(s): Jonathan O. Lipton, Lara M. Boyle, Elizabeth D. Yuan, Kevin J. Hochstrasser, Fortunate F. Chifamba, Ashwin Nathan, Peter T. Tsai, Fred Davis, Mustafa Sahin Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder characterized by mutations in either the TSC1 or TSC2 genes, whose products form a critical inhibitor of the mechanistic target of rapamycin (mTOR). Loss of TSC1/2 gene function renders an mTOR-overactivated state. Clinically, TSC manifests with epilepsy, intellectual disability, autism, and sleep dysfunction. Here, we repo...
Source: Cell Reports - Category: Cytology Source Type: research
Abstract We investigated the clinical phenotypes and genetic mutations in Chinese children diagnosed with tuberous sclerosis complex (TSC). Sequencing of TSC1 and TSC2 genes was performed in 117 children with TSC and their parents. Association of TSC gene mutations with clinical manifestations was investigated. All gene mutations were heterozygous including in 16 patients (13.7%) with mutations in TSC1 gene and 101 patients (86.3%) with mutations in TSC2 gene. Among the 16 patients with TSC1 gene mutations, 15 different types of mutations were found, which included five novel mutations; all patients had skin manif...
Source: Clinical Genetics - Category: Genetics & Stem Cells Authors: Tags: Clin Genet Source Type: research
CONCLUSION: The adaptation for children of the Krebs et al.' NSS scale proved to be valid, especially in children with ASD. PMID: 27349580 [PubMed - as supplied by publisher]
Source: L Encephale - Category: Psychiatry Tags: Encephale Source Type: research
The objectives of this study were to characterize microglial activation in a mouse model of TSC, involving conditional inactivation of the Tsc1 gene predominantly in glial cells (Tsc1GFAPCKO mice), and to test the hypothesis that microglial activation contributes to epileptogenesis in this mouse model. MethodsMicroglial and astrocyte activation was examined in Tsc1GFAPCKO mice by ionized calcium binding adaptor molecule 1 and glial fibrillary acidic protein immunohistochemistry. Cytokine and chemokine expression was evaluated with quantitative polymerase chain reaction. Seizures were monitored by video–electroencepha...
Source: Epilepsia - Category: Neurology Authors: Tags: Full ‐Length Original Research Source Type: research
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