Tuberous Sclerosis Complex Research

An integrated, scaled approach to resolve TSC2 variants of uncertain significance

Abundance scores for 8,891 TSC2 missense variants, plus mTOR pathway activity scores for 391, were calibrated to ACMG/AMP evidence. They putatively reclassify 212 of 276 clinical-cohort missense VUS.

Decoding Lymphangioleiomyomatosis (LAM) Niche Environment via Integrative Analysis of Single Cell Multiomics and Spatial Transcriptomics

This study identifies two distinct LAM subtypes and their microenvironmental interactions using multi-omics and spatial transcriptomics, revealing key regulatory networks and potential therapeutic targets.

The phosphoproteomic landscape of the neurological manifestations in tuberous sclerosis complex

This study performs phosphoproteomic analysis of TSC brain lesions, finding strong mTORC1 activation and widespread mRNA splicing changes in SEGAs but not tubers.

Extracellular Matrix-Induced Genes May Reduce Response to Rapamycin in LAM

This study identifies extracellular matrix genes that reduce rapamycin response in LAM cells and suggests repurposed inhibitors as potential therapies.

mTOR dysregulation induces IL6 and paracrine AT2 cell senescence impeding lung repair in lymphangioleiomyomatosis

This study shows mTOR dysregulation in LAM causes IL6 production and senescence in AT2 cells, impairing lung repair, and suggests targeting IL6 may help.

A Bitopic mTORC Inhibitor Reverses Neural Phenotypes in a Tuberous Sclerosis Complex Murine Model of SEGA-like Hamartomas

This study shows that Rapalink-1, a bitopic mTORC1 inhibitor, reverses neural phenotypes in a TSC SEGA mouse model by reducing hamartoma size and dendrite arbors.

Human TSC2 Mutant Cells Exhibit Aberrations in Early Neurodevelopment Accompanied by Changes in the DNA Methylome

This study shows that TSC2 mutant cells exhibit early neurodevelopmental abnormalities and DNA methylation changes, suggesting early gene regulation disruption in TSC.

Multiparameter Quantitative Analyses of Diagnostic Cells in Brain Tissues from Tuberous Sclerosis Complex

The paper develops a machine learning tool to identify balloon cells in TSC brain tissues using imaging mass cytometry and a custom antibody panel.

Raptor downregulation rescues neuronal phenotypes in mouse models of Tuberous Sclerosis Complex

This study shows that reducing Raptor, a component of mTORC1, improves TSC-related brain phenotypes in mouse models, suggesting it as a potential therapeutic target.

Frequency of FLCN Loss of Function Variants and Birt-Hogg-Dube-Associated Phenotypes in a Healthcare System Population

The paper estimates the prevalence of FLCN pathogenic variants and BHD-related phenotypes in a healthcare population, finding a higher frequency than previously reported and underdiagnosis of BHD.

Tsc1 haploinsufficiency leads to Pax2 dysregulation in the developing murine cerebellum

This paper investigates how Tsc1 haploinsufficiency affects cerebellar development in mice, finding dysregulated Pax2 expression and mTOR pathway changes linked to ASD-like phenotypes.

Genetic Insight into Birt-Hogg-Dube syndrome in Indian patients reveals novel mutations in FLCN

The paper identifies novel FLCN mutations in Indian BHDS patients and highlights the role of MTHFR SNPs in disease diagnosis.

Role of type I interferon signaling and microglia in the abnormal long term potentiation and object place recognition deficits of male mice with a mutation of the Tuberous Sclerosis 2 gene

This study shows that microglia and type I interferon signaling contribute to memory and long-term potentiation deficits in male Tsc2+/- mice, which can be reversed by microglia depletion or interferon receptor manipulation.

Folliculin variants linked to Birt-Hogg-Dube syndrome are targeted for proteasomal degradation

The paper shows that BHD-linked FLCN variants cause loss of function via proteasomal degradation and misfolding, with potential therapeutic implications for stabilization.

A human TSC1 mutation screening platform in GABAergic cortical interneurons for Genotype to Phenotype assessments

This study assesses how TSC1 missense variants affect cortical inhibitory interneurons, revealing some variants can partially restore function while others show specific deficits.

Tsc1-mTOR signaling controls the structure and function of midbrain dopamine neurons

This study shows that loss of Tsc1 in midbrain dopamine neurons leads to structural and functional defects, causing cognitive flexibility deficits that can be mitigated by reducing Raptor.