|
TRICHOTHIODYSTROPHY 2, PHOTOSENSITIVE
|
0.700 |
CausalMutation
|
disease |
CLINVAR |
|
|
|
|
TRICHOTHIODYSTROPHY 2, PHOTOSENSITIVE
|
0.700 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
|
|
|
|
TRICHOTHIODYSTROPHY 2, PHOTOSENSITIVE
|
0.700 |
Biomarker
|
disease |
CTD_human |
|
|
|
|
Trichothiodystrophy Syndromes
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Approximately half of the reported patients with TTD have clinical and cellular photosensitivity associated with mutations in three subunits (ERCC3, ERCC2, GTF2H5) of the basal transcription factor TFHII, which is involved in transcription and nucleotide excision repair.
|
30359777 |
2019 |
|
Trichothiodystrophy Syndromes
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Using quantitative imaging of TFIIH in living mouse cells, we found that these molecules reduce the intracellular concentration of TFIIH and its transcriptional activity to levels similar to that observed in individuals with trichothiodystrophy owing to mutated <i>TTD-A</i> Our results provide a proof of concept of fragment-based drug discovery, demonstrating the utility of small molecules for targeting p8 dimerization to modulate the transcriptional machinery, an approach that may help inform further development in anticancer therapies.
|
30068551 |
2018 |
|
Trichothiodystrophy Syndromes
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
TFIIH-dependent MMP-1 overexpression in trichothiodystrophy leads to extracellular matrix alterations in patient skin.
|
25605938 |
2015 |
|
Trichothiodystrophy Syndromes
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
The subtle transcriptional differences found between various TFIIH variants thus participate in the phenotypic variability observed among XP, XP/CS, and TTD individuals.
|
25620205 |
2015 |
|
Trichothiodystrophy Syndromes
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
The importance of a fully functional XPB is clearly illustrated by the severe clinical consequences associated with inherited defects in XPB including UV-hypersensitive syndromes xeroderma pigmentosum (XP), Cockayne syndrome (CS), combined XP and CS (XP/CS), and trichothiodystrophy (TTD).
|
25641424 |
2015 |
|
Trichothiodystrophy Syndromes
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
To further grasp the molecular mechanisms that govern transcription, we focused our attention on the general transcription factor TFIIH, which gives rise, once mutated, to Trichothiodystrophy (TTD), a rare autosomal premature-ageing disease causing inter alia, metabolic dysfunctions.
|
25340339 |
2014 |
|
Trichothiodystrophy Syndromes
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Our results suggested a link between TTD- but not XP-associated XPD mutations, placental maldevelopment and risk of pregnancy complications, possibly due to impairment of TFIIH-mediated functions in placenta.
|
22234153 |
2012 |
|
Trichothiodystrophy Syndromes
|
0.600 |
Biomarker
|
disease |
BEFREE |
XPB and XPD genetic defects can also cause premature aging with profound neurological defects without increased cancers: Cockayne syndrome (CS) and trichothiodystrophy (TTD).
|
21571596 |
2011 |
|
Trichothiodystrophy Syndromes
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
TTD group A (TTD-A) patients carry mutations in the smallest TFIIH subunit, TTDA, which is an 8-kDa protein that dynamically interacts with TFIIH.
|
21730288 |
2011 |
|
Trichothiodystrophy Syndromes
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Ongoing investigations on TTD are elucidating not only the pathogenesis of the disease, which appears to be mainly related to transcriptional impairment, but also the modalities of NER and transcription in human cells and how TFIIH operates in these two fundamental cellular processes.
|
19931493 |
2010 |
|
Trichothiodystrophy Syndromes
|
0.600 |
Biomarker
|
disease |
BEFREE |
Moreover, mutations in any of these three TFIIH subunits also disturb the overall architecture of the TFIIH complex and its ability to transactivate certain nuclear receptor-responsive genes, explaining in part, some of the TTD phenotypes.
|
19808800 |
2009 |
|
Trichothiodystrophy Syndromes
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Mutations in three of the genes encoding the XPB, XPD and TTDA components of transcription factor TFIIH can result in the clinical phenotype of trichothiodystrophy (TTD).
|
18579452 |
2008 |
|
Trichothiodystrophy Syndromes
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
p8/TTDA overexpression enhances UV-irradiation resistance and suppresses TFIIH mutations in a Drosophila trichothiodystrophy model.
|
19008953 |
2008 |
|
Trichothiodystrophy Syndromes
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Patients with the rare neurodevelopmental repair syndrome known as group A trichothiodystrophy (TTD-A) carry mutations in the gene encoding the p8 subunit of the transcription and DNA repair factor TFIIH.
|
19172752 |
2008 |
|
Trichothiodystrophy Syndromes
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Patients with xeroderma pigmentosum (XP) have a 1,000-fold increase in ultraviolet (UV)-induced skin cancers while trichothiodystrophy (TTD) patients, despite mutations in the same genes, ERCC2 (XPD) or ERCC3 (XPB), are cancer-free.
|
18470933 |
2008 |
|
Trichothiodystrophy Syndromes
|
0.600 |
Biomarker
|
disease |
BEFREE |
Accordingly, defects in specific enzymatic functions typically result in XP, dissociation of the CAK subunit from TFIIH is associated with XP/CS and a more generalized destabilization of TFIIH gives rise to TTD.
|
18077223 |
2008 |
|
Trichothiodystrophy Syndromes
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
These cell lines result from a stable transfection of the XPB-TTD allele into XP complementation group B fibroblasts, from an XP patient who also have clinical abnormalities corresponding to Cockayne's syndrome (CS).
|
15608684 |
2005 |
|
Trichothiodystrophy Syndromes
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
The gene responsible for the TTD-A group of the DNA repair deficient disease trichothiodystrophy has been identified as a small, 8 kDa, component of the transcription factor TFIIH which contributes to the stability and concentration of TFIIH in vivo.
|
15590337 |
2005 |
|
Trichothiodystrophy Syndromes
|
0.600 |
Biomarker
|
disease |
BEFREE |
Moreover, when XPD mutations prevent interaction with the p44 subunit of TFIIH, transactivation directed by certain nuclear receptors is inhibited, regardless of TTD versus XP phenotype, thus explaining the overlapping symptoms.
|
12820975 |
2003 |
|
Trichothiodystrophy Syndromes
|
0.600 |
Biomarker
|
disease |
BEFREE |
Subtle differences in the effects of these different mutations on the many activities of TFIIH and on its stability determine the clinical outcomes, which can be XP, TTD, XP with CS, XP with TTD or COFS.
|
14726016 |
2003 |
|
Trichothiodystrophy Syndromes
|
0.600 |
GermlineCausalMutation
|
disease |
ORPHANET |
We conclude that the severity of the clinical features in TTD patients and the clinical outcome of differentially mutated XPD proteins is likely to depend both on the effects that each mutation has on the stability of TFIIH and on the transcriptional activity of the residual TFIIH complexes.
|
12393803 |
2002 |
|
Trichothiodystrophy Syndromes
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
We have also measured TFIIH levels in cells in which different mutations in the XPD gene are associated with clinical symptoms not of TTD but of the highly cancer-prone disorder xeroderma pigmentosum (XP).
|
12393803 |
2002 |