|
Dyskeratosis Congenita
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
Defects in mTR stability and telomerase activity produced by the Dkc1 A353V mutation in dyskeratosis congenita are rescued by a peptide from the dyskerin TruB domain.
|
22855157 |
2012 |
|
Dyskeratosis Congenita
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
A patient with striking features of both HHS and DKC has a de novo mutation in the DKC1 gene, known to be responsible for DKC.
|
10700698 |
2000 |
|
Dyskeratosis Congenita
|
0.900 |
Biomarker
|
disease |
BEFREE |
The predominant X-linked form of DC results from substitutions in dyskerin, a protein required both for ribosomal RNA (rRNA) pseudouridine modification and for cellular accumulation of telomerase RNA (TER).
|
17015423 |
2006 |
|
Dyskeratosis Congenita
|
0.900 |
Biomarker
|
disease |
BEFREE |
Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome in which the known susceptibility genes (DKC1, TERC, and TERT) belong to the telomere maintenance pathway; patients with DC have very short telomeres.
|
17468339 |
2007 |
|
Dyskeratosis Congenita
|
0.900 |
Biomarker
|
disease |
BEFREE |
The gene mutated in X-linked DC (DKC1) encodes a highly conserved nucleolar protein called dyskerin.
|
14556776 |
2003 |
|
Dyskeratosis Congenita
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
The novel variant detected in the DKC1 gene adds further to the existing scientific literature on the genotype-phenotype correlation of DC, and has important implications for the clinical and molecular characterization of the disease.
|
29801475 |
2018 |
|
Dyskeratosis Congenita
|
0.900 |
Biomarker
|
disease |
BEFREE |
Inherited SHQ1 mutations impair interaction with NAP57/dyskerin, a major target in dyskeratosis congenita.
|
29178645 |
2017 |
|
Dyskeratosis Congenita
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
The social amoeba <i>Dictyostelium discoideum</i> contains a gene coding for a dyskerin homologous protein.In this article <i>D. discoideum</i> mutant strains that have mutations corresponding to mutations found in dyskeratosis congenita patients are described.
|
31717312 |
2019 |
|
Dyskeratosis Congenita
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
We have also identified a dyskeratosis congenita mutation cluster site within a modeled dyskerin structure.
|
16427014 |
2006 |
|
Dyskeratosis Congenita
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
Inherited mutations inactivating dyskerin cause dyskeratosis congenita, a syndrome with progeroid features characterised by skin defects and haematopoiesis failure, as well as cancer susceptibility.
|
19755982 |
2009 |
|
Dyskeratosis Congenita
|
0.900 |
Biomarker
|
disease |
BEFREE |
Dyskerin is therefore thought to function in the processing of pre-rRNA and of the hTR, strengthening the notion that the underlying mechanism of DKC is a premature senescence of cells, especially of the rapidly dividing epithelial and hemopoietic cells.
|
10903840 |
2000 |
|
Dyskeratosis Congenita
|
0.900 |
Biomarker
|
disease |
BEFREE |
Subsequently, dyskerin and TERC were shown to closely associate with each other in the telomerase complex, and DC has since come to be regarded as a telomerase deficiency disorder characterised by shorter telomeres.
|
15613268 |
2004 |
|
Dyskeratosis Congenita
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
To understand the role of dyskerin in hTR accumulation, we analyzed X-DC substitutions K39E and K43E in the poorly characterized dyskerin N-terminus, and A353V within the canonical RNA binding domain (the PUA).
|
30931479 |
2019 |
|
Dyskeratosis Congenita
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
We used human embryonic stem cells (hESCs) with a common dyskerin mutation (DKC1_A353V), which have defective telomere maintenance and reduced definitive hematopoietic potential, to understand the effects of reducing EXOSC3 activity, or silencing PAPD5-mediated oligoadenylation, on hematopoietic progenitor specification and function in DC.
|
30728146 |
2019 |
|
Dyskeratosis Congenita
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
Identification of novel DKC1 mutations in patients with dyskeratosis congenita: implications for pathophysiology and diagnosis.
|
11379875 |
2001 |
|
Dyskeratosis Congenita
|
0.900 |
AlteredExpression
|
disease |
BEFREE |
These data identify decreased dyskerin levels as a novel mechanism of DC, and indicate that intact dyskerin levels, in the absence of coding mutations, are critical for telomerase RNA stability and for in vivo telomere maintenance.
|
21415081 |
2011 |
|
Dyskeratosis Congenita
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
Genotype-phenotype correlations show genes responsible for X-linked (DKC1) and severe recessive childhood dyskeratosis congenita, typically with associated mucocutaneous features, and others (TERC and TERT) for more subtle presentation as telomeropathy in adults, in which multiorgan failure may be prominent.
|
25237198 |
2014 |
|
Dyskeratosis Congenita
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
Extended culture of DKC1-mutant iPSCs leads to progressive telomere shortening and eventual loss of self-renewal, indicating that a similar process occurs in tissue stem cells in dyskeratosis congenita patients.
|
21602826 |
2011 |
|
Dyskeratosis Congenita
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
Five different missense mutations in five unrelated patients were subsequently identified in XAP101, indicating that it is the gene responsible for X-linked DKC (DKC1).
|
9590285 |
1998 |
|
Dyskeratosis Congenita
|
0.900 |
Biomarker
|
disease |
BEFREE |
Here we discuss these results in terms of the role of dyskerin in telomere maintenance and the possible role that the DNA damage response plays in the pathogenesis of DC.
|
19106610 |
2009 |
|
Dyskeratosis Congenita
|
0.900 |
Biomarker
|
disease |
BEFREE |
The gene for the X-linked form of DC has been identified on Xq28 and designated as DKC1.
|
11641517 |
2001 |
|
Dyskeratosis Congenita
|
0.900 |
AlteredExpression
|
disease |
BEFREE |
GSE24.2 peptide and a short derivative GSE4 peptide corresponding to an internal domain of Dyskerin have proved to induce telomerase activity, decrease oxidative stress, and protect from DNA damage in dyskeratosis congenita (DC) cells.
|
30670828 |
2019 |
|
Dyskeratosis Congenita
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
Identification of a novel mutation in DKC1 in dyskeratosis congenita.
|
18802941 |
2009 |
|
Dyskeratosis Congenita
|
0.900 |
Biomarker
|
disease |
BEFREE |
All eight known disease-causing genes in DC (DKC1, TERC, TERT, NOP10, NHP2, TINF2, C16orf57, and TCAB1) were screened for mutations.
|
22814958 |
2012 |
|
Dyskeratosis Congenita
|
0.900 |
Biomarker
|
disease |
BEFREE |
The subsequent identification of mutations in the telomerase RNA component (TERC) of autosomal dominant DC patients together with the discovery that both TERC and the DKC1-encoded protein, dyskerin, are closely associated in the telomerase complex have suggested that the pathophysiology of DC predominantly relates to defective telomere maintenance.
|
15917199 |
2005 |