ArticleBrain pathology (Zurich, Switzerland)2010
Analysis of TSC cortical tubers by deep sequencing of TSC1, TSC2 and KRAS demonstrates that small second-hit mutations in these genes are rare events.
Article in Brain pathology (Zurich, Switzerland), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 2 of them syntheses that pooled it.
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Who cites it
76 citing papers in PubMed, 2 syntheses or guidelines pooled it, 121 citations in OpenAlex.
- The association of neurodevelopmental abnormalities, congenital heart and renal defects in a tuberous sclerosis complex patient cohort.BMC medicine · 2022Pooled it
- Genotype-phenotype correlations in focal malformations of cortical development: a pathway to integrated pathological diagnosis in epilepsy surgery.Brain pathology (Zurich, Switzerland) · 2019Pooled it
- Article
- The critical role of the proto-oncogene c-Kit in TSC renal cystogenesis.EMBO molecular medicine · 2026Article
- AAV hamartin gene therapy in a stochastic, cerebral mouse model of tuberous sclerosis type 1.Molecular therapy. Methods & clinical development · 2025Article
- Human TSC2 mutant cells exhibit aberrations in early neurodevelopment accompanied by changes in the DNA Methylome.Human molecular genetics · 2025Article
- Role of Extracellular Vesicles in TSC Renal Cystogenesis.International journal of molecular sciences · 2025Article
- Neuronal cell type specific roles for Nprl2 in neurodevelopmental disorder-relevant behaviors.Neurobiology of disease · 2025Article
- Somatic DNA Variants in Epilepsy Surgery Brain Samples from Patients with Lesional Epilepsy.International journal of molecular sciences · 2025Article
- Somatic Mosaicism in Brain Disorders.Annual review of pathology · 2025Review
- The molecular genetics of PI3K/PTEN/AKT/mTOR pathway in the malformations of cortical development.Genes & diseases · 2024Review
- Human TSC2 Mutant Cells Exhibit Aberrations in Early Neurodevelopment Accompanied by Changes in the DNA Methylome.bioRxiv : the preprint server for biology · 2024Article
- Multi-dimensional Insight into the Coexistence of Pathogenic Genes for ADAR1 and TSC2: Careful Consideration is Essential for Interpretation of ADAR1 Variants.Biochemical genetics · 2024Article
- Somatic variants as a cause of drug-resistant epilepsy including mesial temporal lobe epilepsy with hippocampal sclerosis.Epilepsia · 2024Article
- mTOR Pathway Somatic Pathogenic Variants in Focal Malformations of Cortical Development: Novel Variants, Topographic Mapping, and Clinical Outcomes.Neurology. Genetics · 2023Article
- Specific Features of Focal Cortical Dysplasia in Tuberous Sclerosis Complex.Current issues in molecular biology · 2023Review
- Cytogenomic epileptology.Molecular cytogenetics · 2023Review
- Modeling genetic mosaicism of the mammalian target of rapamycin pathway in the cerebral cortex.Frontiers in mammal science · 2023Article
- Neurodevelopmental disorders: 2023 update.Free neuropathology · 2023Article
- Somatic mosaicism in the diseased brain.Molecular cytogenetics · 2022Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Tuberous sclerosis complex (TSC) is an often severe neurocutaneous syndrome. Cortical tubers are the predominant neuropathological finding in TSC, and their number and location has been shown to correlate roughly with the severity of neurologic features in TSC. Past studies have shown that genomic deletion events in TSC1 or TSC2 are very rare in tubers, and suggested the potential involvement of the MAPK pathway in their pathogenesis. We used deep sequencing to assess all coding exons of TSC1 and TSC2, and the activating mutation hot spots within KRAS in 46 tubers from TSC patients. Germline heterozygous mutations were identified in 81% of tubers. The same secondary mutation in TSC2 was identified in six tuber samples from one individual. Further study showed that this second hit mutation was widely distributed in the cortex from one cerebral hemisphere of this individual at frequencies up to 10%. No other secondary mutations were found in the other 40 tubers analyzed. These data indicate that small second hit mutations in any of these three genes are very rare in TSC tubers. However, in one TSC individual, a second hit TSC2 point mutation occurred early during brain development, and likely contributed to tuber formation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.