Search results for "Dyskeratosis"
showing 9 items of 9 documents
Acute telomerase components depletion triggers oxidative stress as an early event previous to telomeric shortening
2018
Loss of function of dyskerin (DKC1), NOP10 and TIN2 are responsible for different inheritance patterns of Dyskeratosis congenita (DC; ORPHA1775). They are key components of telomerase (DKC1 and NOP10) and shelterin (TIN2), and play an important role in telomere homeostasis. They participate in several fundamental cellular processes by contributing to Dyskeratosis congenita through mechanisms that are not fully understood. Presence of oxidative stress was postulated to result from telomerase ablation. However, the resulting disturbed redox status can promote telomere attrition by generating a vicious circle, which promotes cellular senescence. This fact prompted us to study if acute loss of …
Acute depletion of telomerase components DKC1 and NOP10 induces oxidative stress and disrupts ribosomal biogenesis via NPM1 and activation of the P53…
2020
Mutations in DKC1, NOP10, and TINF2 genes, coding for proteins in telomerase and shelterin complexes, are responsible for diverse diseases known as telomeropathies and ribosomopathies, including dyskeratosis congenita (DC, ORPHA 1775). These genes contribute to the DC phenotype through mechanisms that are not completely understood. We previously demonstrated in models of DC that oxidative stress is an early and independent event that occurs prior to telomere shortening. To clarify the mechanisms that induce oxidative stress, we silenced genes DKC1, NOP10, and TINF2 with siRNA technology. With RNA array hybridisation, we found several altered pathways for each siRNA model. Afterwards, we ide…
Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus
2012
Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γ 3H2AX-positive cells in cell lines derived from two affected individual…
Focal palmoplantar and gingival keratosis ? A rare genodermatoses : case report
2020
Focal palmoplantar and gingival keratosis syndrome is a rare dominant inherited disease with an early onset in life. Clinically, the condition is characterized by pressure related thickening of the epidermis of the palms and soles, usually accompanied by pain and different levels of skin involvement and thickness between patients. Recently, we observed a 38-year-old woman with multiple non-removable, painless white plaques of variable size and thickness on the attached gingiva and a white plaque widespread across the hard palate. By further questioning, the patient comments that she has thick yellowish focal plaques in both soles of her feet. Histopathological analysis revealed a hyperplast…
Zinsser-Cole-Engmann syndrome: A rare case report with literature review
2014
Zinsser-Cole-Engmann syndrome, more commonly known as Dyskeratosis Congenita, is a heritable genodermatosis having an estimated incidence of 1 in 1 million people. It is important for an oral physician to be aware of this condition as oral leukoplakia occurs in this condition as part of a classic triad along with reticulate skin pigmentation and nail dystrophy. Besides these, there may be myriad multisystem involvement as well. These individuals have a high predilection for developing malignancies as well as other grave life-threatening conditions. Timely diagnosis and management of these cases may help improve their morbidity and mortality, for which oral physicians can play a major role i…
Corneal Epithelial Stem Cells-Physiology, Pathophysiology and Therapeutic Options.
2021
In the human cornea, regeneration of the epithelium is regulated by the stem cell reservoir of the limbus, which is the marginal region of the cornea representing the anatomical and functional border between the corneal and conjunctival epithelium. In support of this concept, extensive limbal damage, e.g., by chemical or thermal injury, inflammation, or surgery, may induce limbal stem cell deficiency (LSCD) leading to vascularization and opacification of the cornea and eventually vision loss. These acquired forms of limbal stem cell deficiency may occur uni- or bilaterally, which is important for the choice of treatment. Moreover, a variety of inherited diseases, such as congenital aniridia…
Expression of the genetic suppressor element 24.2 (GSE24.2) decreases DNA damage and oxidative stress in X-linked dyskeratosis congenita cells.
2014
This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.
Systematic search for neutropenia should be part of the first screening in patients with poikiloderma.
2011
Poikiloderma occurs in a number of hereditary syndromes, the best known of which is Rothmund-Thomson syndrome (RTS). Differential diagnoses include Dyskeratosis Congenita (DC) with high genetic heterogeneity and Clericuzio-type Poikiloderma with Neutropenia (CPN) due to mutations in the C16orf57 gene. Mutations in the RECQL4 gene are only observed in two thirds of RTS patients. In this study, 10 patients referred for syndromic poikiloderma and negative for RECQL4 sequencing analysis were investigated for C16orf57 mutations. Two C16orf57 heterozygous nonsense mutations (p.W81X and p.Y89X) were identified in a 5-year-old female child presenting with generalized poikiloderma, dental dysplasia,…
Dyskeratosis congenita: Report of a case with literature review
2007
Leukoplakic lesion is not uncommon in clinical practice but its occurrence as a component of a syndrome is rare. Dyskeratosis congenita is a rare genodermatosis, which is characterized by triad of skin pigmentation, nail dystrophy and leukoplakic lesion in the oral cavity. It is important for dentists to now about Dyskeratosis Congenita because these leukoplakic lesions can spontaneously undergo malignant transformation. Majority of cases have been reported in dermatology or pediatrics literature whereas only few reports have appeared in dental literature. The purpose of reporting this case with review of recent literature is to create better awareness among dentists about the multisystem m…