dyskeratosis congenita

Summary

Summary: A predominantly X-linked recessive syndrome characterized by a triad of reticular skin pigmentation, nail dystrophy and leukoplakia of mucous membranes. Oral and dental abnormalities may also be present. Complications are a predisposition to malignancy and bone marrow involvement with pancytopenia. (from Int J Paediatr Dent 2000 Dec;10(4):328-34) The X-linked form is also known as Zinsser-Cole-Engman syndrome and involves the gene which encodes a highly conserved protein called dyskerin.

Top Publications

  1. Beier F, Foronda M, Martinez P, Blasco M. Conditional TRF1 knockout in the hematopoietic compartment leads to bone marrow failure and recapitulates clinical features of dyskeratosis congenita. Blood. 2012;120:2990-3000 pubmed publisher
    ..b>Dyskeratosis congenita is characterized by a mucocutaneous triad, bone marrow failure (BMF), and presence of short telomeres ..
  2. Gourronc F, Robertson m, Herrig A, Lansdorp P, Goldman F, Klingelhutz A. Proliferative defects in dyskeratosis congenita skin keratinocytes are corrected by expression of the telomerase reverse transcriptase, TERT, or by activation of endogenous telomerase through expression of papillomavirus E6/E7 or the telomerase RNA c. Exp Dermatol. 2010;19:279-88 pubmed publisher
    b>Dyskeratosis congenita (DC) is characterized by the triad of reticulate skin pigmentation, nail dystrophy and leukoplakia...
  3. He J, Navarrete S, Jasinski M, Vulliamy T, Dokal I, Bessler M, et al. Targeted disruption of Dkc1, the gene mutated in X-linked dyskeratosis congenita, causes embryonic lethality in mice. Oncogene. 2002;21:7740-4 pubmed
    b>Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome associated with increased cancer susceptibility...
  4. Savage S, Alter B. Dyskeratosis congenita. Hematol Oncol Clin North Am. 2009;23:215-31 pubmed publisher
    b>Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome characterized clinically by the triad of abnormal nails, reticular skin pigmentation, and oral leukoplakia, and is associated with high risk of developing aplastic ..
  5. Li S, Duan J, Li D, Ma S, Ye K. Structure of the Shq1-Cbf5-Nop10-Gar1 complex and implications for H/ACA RNP biogenesis and dyskeratosis congenita. EMBO J. 2011;30:5010-20 pubmed publisher
    ..The structure shows that dyskeratosis congenita mutations found in the CTE of human Cbf5 likely interfere with Shq1 binding...
  6. Erduran E, Hacisalihoglu S, Ozoran Y. Treatment of dyskeratosis congenita with granulocyte-macrophage colony-stimulating factor and erythropoietin. J Pediatr Hematol Oncol. 2003;25:333-5 pubmed
    b>Dyskeratosis congenita (DC) is a rare inherited disorder characterized by reticulate skin pigmentation, nail dystrophy, mucosal leucoplakia, and bone marrow failure. Pancytopenia is difficult to manage in patients with this disorder...
  7. Westin E, Chavez E, Lee K, Gourronc F, Riley S, Lansdorp P, et al. Telomere restoration and extension of proliferative lifespan in dyskeratosis congenita fibroblasts. Aging Cell. 2007;6:383-94 pubmed
    b>Dyskeratosis congenita (DC), an inherited bone marrow failure syndrome, is caused by defects in telomerase...
  8. Mason P, Bessler M. The genetics of dyskeratosis congenita. Cancer Genet. 2011;204:635-45 pubmed publisher
    b>Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome associated with characteristic mucocutaneous features and a variable series of other somatic abnormalities...
  9. Machado Pinilla R, Carrillo J, Manguan García C, Sastre L, Mentzer A, Gu B, et al. 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. Clin Transl Oncol. 2012;14:755-63 pubmed publisher
    The predominant X-linked form of dyskeratosis congenita results from mutations in dyskerin, a protein required for ribosomal RNA modification that is also a component of the telomerase complex...

More Information

Publications62

  1. Yaghmai R, Kimyai Asadi A, Rostamiani K, Heiss N, Poustka A, Eyaid W, et al. Overlap of dyskeratosis congenita with the Hoyeraal-Hreidarsson syndrome. J Pediatr. 2000;136:390-3 pubmed
    X-linked dyskeratosis congenita (DKC) is characterized by mucosal leukoplakia and ulcerations, skin abnormalities, nail dystrophy, and pancytopenia...
  2. Vulliamy T, Dokal I. Dyskeratosis congenita: the diverse clinical presentation of mutations in the telomerase complex. Biochimie. 2008;90:122-30 pubmed
    b>Dyskeratosis congenita is an inherited syndrome characterised by mucocutaneous features, bone marrow failure, an increased risk of malignancy and other somatic abnormalities...
  3. Nelson N, Bertuch A. Dyskeratosis congenita as a disorder of telomere maintenance. Mutat Res. 2012;730:43-51 pubmed publisher
    Since 1998, there have been great advances in our understanding of the pathogenesis of dyskeratosis congenita (DC), a rare inherited bone marrow failure and cancer predisposition syndrome with prominent mucocutaneous abnormalities and ..
  4. Mason P, Wilson D, Bessler M. Dyskeratosis congenita -- a disease of dysfunctional telomere maintenance. Curr Mol Med. 2005;5:159-70 pubmed
    b>Dyskeratosis congenita (DC) is a rare inherited bone marrow failure syndrome associated with abnormalities of the skin, fingernails, and tongue...
  5. Cerone M, Ward R, Londono Vallejo J, Autexier C. Telomerase RNA mutated in autosomal dyskeratosis congenita reconstitutes a weakly active telomerase enzyme defective in telomere elongation. Cell Cycle. 2005;4:585-9 pubmed
    b>Dyskeratosis congenita (DC) is a rare multi-system syndrome characterized by nail dystrophy, abnormal skin pigmentation and mucosal leukoplakia...
  6. Walne A, Bhagat T, Kirwan M, Gitiaux C, Desguerre I, Leonard N, et al. Mutations in the telomere capping complex in bone marrow failure and related syndromes. Haematologica. 2013;98:334-8 pubmed publisher
    b>Dyskeratosis congenita and its variants have overlapping phenotypes with many disorders including Coats plus, and their underlying pathology is thought to be one of defective telomere maintenance...
  7. Aslan D, Akata R, Holme H, Vulliamy T, Dokal I. Limbal stem cell deficiency in patients with inherited stem cell disorder of dyskeratosis congenita. Int Ophthalmol. 2012;32:615-22 pubmed publisher
    The aim of this study is to present the limbal stem cell deficiency (LSCD) cases with features resembling dyskeratosis congenita (DC), a heritable disease of stem cells principally caused by telomerase deficiency...
  8. Savage S, Dokal I, Armanios M, Aubert G, Cowen E, Domingo D, et al. Dyskeratosis congenita: the first NIH clinical research workshop. Pediatr Blood Cancer. 2009;53:520-3 pubmed publisher
    b>Dyskeratosis congenita (DC) is a heterogeneous inherited bone marrow failure syndrome, characterized by abnormally short telomeres and mutations in telomere biology genes...
  9. Fu D, Collins K. Distinct biogenesis pathways for human telomerase RNA and H/ACA small nucleolar RNAs. Mol Cell. 2003;11:1361-72 pubmed
    ..This telomerase-specific hTR element is mutated in dyskeratosis congenita, and the disease-associated hTR substitution impairs RNA accumulation...
  10. Dokal I. Dyskeratosis congenita in all its forms. Br J Haematol. 2000;110:768-79 pubmed
  11. Reimann C, Kloeckener Gruissem B, Niemeyer C, Vanscheidt W. Late manifestation of dyskeratosis congenita presenting as chronic dermal ulcer in a 37-year-old man. J Eur Acad Dermatol Venereol. 2008;22:897-8 pubmed
  12. Goldman F, Bouarich R, Kulkarni S, Freeman S, DU H, Harrington L, et al. The effect of TERC haploinsufficiency on the inheritance of telomere length. Proc Natl Acad Sci U S A. 2005;102:17119-24 pubmed
    ..Loss of telomere function causes cell-cycle arrest or cell death. Autosomal dominant dyskeratosis congenita (AD DC), a rare inherited bone marrow failure syndrome, is caused by mutations in TERC, the RNA component ..
  13. Kirwan M, Dokal I. Dyskeratosis congenita, stem cells and telomeres. Biochim Biophys Acta. 2009;1792:371-9 pubmed publisher
    b>Dyskeratosis congenita (DC) is a multi-system disorder which in its classical form is characterised by abnormalities of the skin, nails and mucous membranes. In approximately 80% of cases, it is associated with bone marrow dysfunction...
  14. Vulliamy T, Marrone A, Szydlo R, Walne A, Mason P, Dokal I. Disease anticipation is associated with progressive telomere shortening in families with dyskeratosis congenita due to mutations in TERC. Nat Genet. 2004;36:447-9 pubmed
    ..component of this reverse transcriptase is mutated in the bone marrow failure syndrome autosomal dominant dyskeratosis congenita. Here we show that disease anticipation is observed in families with this disease and that this is ..
  15. Armanios M. Syndromes of telomere shortening. Annu Rev Genomics Hum Genet. 2009;10:45-61 pubmed publisher
    ..Telomere-mediated disease was initially identified in the context of dyskeratosis congenita, a rare syndrome of premature aging...
  16. Giri N, Pitel P, Green D, Alter B. Splenic peliosis and rupture in patients with dyskeratosis congenita on androgens and granulocyte colony-stimulating factor. Br J Haematol. 2007;138:815-7 pubmed
  17. Pavesi E, Avondo F, Aspesi A, Quarello P, Rocci A, Vimercati C, et al. Analysis of telomeres in peripheral blood cells from patients with bone marrow failure. Pediatr Blood Cancer. 2009;53:411-6 pubmed publisher
    The determination of telomere length is useful for the characterization of dyskeratosis congenita (DC) and of aplastic anemias (AA) as well as hematological malignancies...
  18. Tsilou E, Giri N, Weinstein S, Mueller C, Savage S, Alter B. Ocular and orbital manifestations of the inherited bone marrow failure syndromes: Fanconi anemia and dyskeratosis congenita. Ophthalmology. 2010;117:615-22 pubmed publisher
    ..The 4 most frequent syndromes are Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SDS)...
  19. Alter B, Rosenberg P, Giri N, Baerlocher G, Lansdorp P, Savage S. Telomere length is associated with disease severity and declines with age in dyskeratosis congenita. Haematologica. 2012;97:353-9 pubmed publisher
    b>Dyskeratosis congenita is a cancer-prone bone marrow failure syndrome caused by aberrations in telomere biology. We studied 65 patients with dyskeratosis congenita and 127 unaffected relatives...
  20. Alter B, Baerlocher G, Savage S, Chanock S, Weksler B, Willner J, et al. Very short telomere length by flow fluorescence in situ hybridization identifies patients with dyskeratosis congenita. Blood. 2007;110:1439-47 pubmed
    b>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...
  21. de la Fuente J, Dokal I. Dyskeratosis congenita: advances in the understanding of the telomerase defect and the role of stem cell transplantation. Pediatr Transplant. 2007;11:584-94 pubmed
  22. Montanaro L, Chillà A, Trere D, Pession A, Govoni M, Tazzari P, et al. Increased mortality rate and not impaired ribosomal biogenesis is responsible for proliferative defect in dyskeratosis congenita cell lines. J Invest Dermatol. 2002;118:193-8 pubmed
    X-linked dyskeratosis congenita is a rare inherited disorder mainly characterized by progressive changes in proliferating epidermal, mucosal, and bone marrow tissues that commonly emerge after 10 y of life...
  23. Heiss N, Girod A, Salowsky R, Wiemann S, Pepperkok R, Poustka A. Dyskerin localizes to the nucleolus and its mislocalization is unlikely to play a role in the pathogenesis of dyskeratosis congenita. Hum Mol Genet. 1999;8:2515-24 pubmed
    Mutations in the DKC1 gene are responsible for causing the bone marrow failure syndrome, dyskeratosis congenita (DKC; OMIM 305000). The majority of mutations identified to date are missense mutations and are clustered in exons 3, 4 and 11...
  24. Machado Pinilla R, Sanchez Perez I, Murguia J, Sastre L, Perona R. A dyskerin motif reactivates telomerase activity in X-linked dyskeratosis congenita and in telomerase-deficient human cells. Blood. 2008;111:2606-14 pubmed
    Dyskerin gene is mutated in patients with X-linked dyskeratosis congenita (X-DC), which results in greatly reduced levels of telomerase activity...
  25. Kirwan M, Dokal I. Dyskeratosis congenita: a genetic disorder of many faces. Clin Genet. 2008;73:103-12 pubmed
    b>Dyskeratosis congenita (DC) is an inherited syndrome exhibiting marked clinical and genetic heterogeneity...
  26. Parry E, Alder J, Lee S, Phillips J, Loyd J, Duggal P, et al. Decreased dyskerin levels as a mechanism of telomere shortening in X-linked dyskeratosis congenita. J Med Genet. 2011;48:327-33 pubmed publisher
    b>Dyskeratosis congenita (DC) is a premature ageing syndrome characterised by short telomeres...
  27. Marrone A, Sokhal P, Walne A, Beswick R, Kirwan M, Killick S, et al. Functional characterization of novel telomerase RNA (TERC) mutations in patients with diverse clinical and pathological presentations. Haematologica. 2007;92:1013-20 pubmed
    ..RNA component) and TERT (telomerase reverse transcriptase) mutations found in autosomal dominant dyskeratosis congenita (DC) and aplastic anemia (AA) shows that telomerase function is defective and that this is associated with ..
  28. Goldfarb S, Sullivan K, Jyonouchi S. A patient with X-linked dyskeratosis congenita presenting with bronchiolitis obliterans requiring lung transplantation and immunodeficiency. Pediatr Pulmonol. 2013;48:91-3 pubmed publisher
    b>Dyskeratosis congenita (DKC) is a syndrome characterized by immunodeficiency, bone marrow (BM) failure, somatic abnormalities, and predisposition to malignancy, resulting from mutations in proteins involved in maintenance of telomeres...
  29. Carrillo J, Martinez P, Solera J, Moratilla C, Gonzalez A, Manguan Garcia C, et al. High resolution melting analysis for the identification of novel mutations in DKC1 and TERT genes in patients with dyskeratosis congenita. Blood Cells Mol Dis. 2012;49:140-6 pubmed publisher
    b>Dyskeratosis congenita (DC) is a rare inherited bone-marrow failure syndrome with high clinical heterogeneity...
  30. Fogarty P, Yamaguchi H, Wiestner A, Baerlocher G, Sloand E, Zeng W, et al. Late presentation of dyskeratosis congenita as apparently acquired aplastic anaemia due to mutations in telomerase RNA. Lancet. 2003;362:1628-30 pubmed
    ..This gene is abnormal in some kindreds with dyskeratosis congenita. Individuals in our families with mutated TERC did not have physical signs of dyskeratosis congenita, and ..
  31. Touzot F, Gaillard L, Vasquez N, Le Guen T, Bertrand Y, Bourhis J, et al. Heterogeneous telomere defects in patients with severe forms of dyskeratosis congenita. J Allergy Clin Immunol. 2012;129:473-82, 482.e1-3 pubmed publisher
    ..In human subjects telomere maintenance deficiency leads to dyskeratosis congenita (DC), a rare genetic disorder characterized by progressive bone marrow failure, accelerated aging, and ..
  32. Ballew B, Savage S. Updates on the biology and management of dyskeratosis congenita and related telomere biology disorders. Expert Rev Hematol. 2013;6:327-37 pubmed publisher
    b>Dyskeratosis congenita (DC) is a cancer-prone inherited bone marrow failure syndrome caused by aberrant telomere biology...
  33. Westin E, Aykin Burns N, Buckingham E, Spitz D, Goldman F, Klingelhutz A. The p53/p21(WAF/CIP) pathway mediates oxidative stress and senescence in dyskeratosis congenita cells with telomerase insufficiency. Antioxid Redox Signal. 2011;14:985-97 pubmed publisher
    ..genes for telomere binding proteins or components of telomerase give rise to the premature aging disorder dyskeratosis congenita (DC), which is characterized by extremely short telomeres and an aging phenotype...
  34. Bellodi C, Kopmar N, Ruggero D. Deregulation of oncogene-induced senescence and p53 translational control in X-linked dyskeratosis congenita. EMBO J. 2010;29:1865-76 pubmed publisher
    ..One example is X-linked dyskeratosis congenita (X-DC) in which the DKC1 gene, encoding for an enzyme that modifies ribosomal RNA, is found to be mutated...
  35. Agarwal S, Loh Y, McLoughlin E, Huang J, Park I, Miller J, et al. Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients. Nature. 2010;464:292-6 pubmed publisher
    Patients with dyskeratosis congenita (DC), a disorder of telomere maintenance, suffer degeneration of multiple tissues...
  36. He H, Wang Y, Guo X, Ramchandani S, Ma J, Shen M, et al. Pot1b deletion and telomerase haploinsufficiency in mice initiate an ATR-dependent DNA damage response and elicit phenotypes resembling dyskeratosis congenita. Mol Cell Biol. 2009;29:229-40 pubmed publisher
    ..Interestingly, these phenotypes closely resemble those found in the human disease dyskeratosis congenita (DC), an inherited syndrome characterized by bone marrow failure, hyperpigmentation, and nail dystrophy...
  37. Goldman F, Aubert G, Klingelhutz A, Hills M, Cooper S, Hamilton W, et al. Characterization of primitive hematopoietic cells from patients with dyskeratosis congenita. Blood. 2008;111:4523-31 pubmed publisher
    b>Dyskeratosis congenita (DC) is an inherited bone marrow (BM) failure syndrome associated with mutations in telomerase genes and the acquisition of shortened telomeres in blood cells...
  38. Alter B, Giri N, Savage S, Peters J, Loud J, Leathwood L, et al. Malignancies and survival patterns in the National Cancer Institute inherited bone marrow failure syndromes cohort study. Br J Haematol. 2010;150:179-88 pubmed publisher
    Fanconi anaemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anaemia (DBA), and Shwachman-Diamond syndrome (SDS) comprise major inherited bone marrow failure syndromes (IBMFS)...
  39. Vulliamy T, Knight S, Mason P, Dokal I. Very short telomeres in the peripheral blood of patients with X-linked and autosomal dyskeratosis congenita. Blood Cells Mol Dis. 2001;27:353-7 pubmed
    b>Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome in which patients undergo premature ageing and have a predisposition to malignancy...
  40. Hartwig F, Collares T. Telomere dysfunction and tumor suppression responses in dyskeratosis congenita: balancing cancer and tissue renewal impairment. Ageing Res Rev. 2013;12:642-52 pubmed publisher
    b>Dyskeratosis congenita (DC) encompasses a large spectrum of diseases and clinical manifestations generally related to premature aging, including bone marrow failure and cancer predisposition...
  41. Collins K, Mitchell J. Telomerase in the human organism. Oncogene. 2002;21:564-79 pubmed
    ..We discuss how our current perspectives on telomerase function could be applied to improving human health. ..
  42. Marrone A, Stevens D, Vulliamy T, Dokal I, Mason P. Heterozygous telomerase RNA mutations found in dyskeratosis congenita and aplastic anemia reduce telomerase activity via haploinsufficiency. Blood. 2004;104:3936-42 pubmed
    Mutations in TERC, encoding the RNA component of telomerase, have been found in autosomal dominant dyskeratosis congenita (DC) and aplastic anemia (AA)...
  43. Marrone A, Walne A, Dokal I. Dyskeratosis congenita: telomerase, telomeres and anticipation. Curr Opin Genet Dev. 2005;15:249-57 pubmed
    b>Dyskeratosis congenita (DC) is a rare bone marrow failure syndrome that displays marked clinical and genetic heterogeneity...
  44. Yoon A, Peng G, Brandenburger Y, Brandenburg Y, Zollo O, Xu W, et al. Impaired control of IRES-mediated translation in X-linked dyskeratosis congenita. Science. 2006;312:902-6 pubmed publisher
    ..DKC1 is mutated in people with X-linked dyskeratosis congenita (X-DC), a disease characterized by bone marrow failure, skin abnormalities, and increased susceptibility ..
  45. Trahan C, Martel C, Dragon F. Effects of dyskeratosis congenita mutations in dyskerin, NHP2 and NOP10 on assembly of H/ACA pre-RNPs. Hum Mol Genet. 2010;19:825-36 pubmed publisher
    b>Dyskeratosis congenita (DC) is a rare genetic syndrome that gives rise to a variety of disorders in affected individuals. Remarkably, all causative gene mutations identified to date share a link to telomere/telomerase biology...
  46. Field J, Mason P, An P, Kasai Y, McLellan M, Jaeger S, et al. Low frequency of telomerase RNA mutations among children with aplastic anemia or myelodysplastic syndrome. J Pediatr Hematol Oncol. 2006;28:450-3 pubmed
    Mutations in TERC, the RNA component of telomerase, result in autosomal dominant dyskeratosis congenita (DC), a rare bone marrow failure syndrome...
  47. Keller R, Gagne K, Usmani G, Asdourian G, Williams D, Hofmann I, et al. CTC1 Mutations in a patient with dyskeratosis congenita. Pediatr Blood Cancer. 2012;59:311-4 pubmed publisher
    b>Dyskeratosis congenita (DC) is a rare inherited bone marrow failure syndrome caused by mutations in seven genes involved in telomere biology, with approximately 50% of cases remaining genetically uncharacterized...
  48. Vulliamy T, Marrone A, Knight S, Walne A, Mason P, Dokal I. Mutations in dyskeratosis congenita: their impact on telomere length and the diversity of clinical presentation. Blood. 2006;107:2680-5 pubmed
    The two genes mutated in the bone marrow failure syndrome dyskeratosis congenita (DC) both encode components of the telomerase complex responsible for maintaining the ends of chromosomes in stem cells and in the germ line...
  49. Davidovich E, Eimerl D, Aker M, Shapira J, Peretz B. Dyskeratosis congenita: dental management of a medically complex child. Pediatr Dent. 2005;27:244-8 pubmed
    b>Dyskeratosis congenita (DKC) is a rare syndrome characterized by cutaneous hyperpigmentation, nail dystrophy, leukoplakia, and pancytopenia...
  50. Vulliamy T, Beswick R, Kirwan M, Marrone A, Digweed M, Walne A, et al. Mutations in the telomerase component NHP2 cause the premature ageing syndrome dyskeratosis congenita. Proc Natl Acad Sci U S A. 2008;105:8073-8 pubmed publisher
    b>Dyskeratosis congenita is a premature aging syndrome characterized by muco-cutaneous features and a range of other abnormalities, including early greying, dental loss, osteoporosis, and malignancy...
  51. Walne A, Vulliamy T, Beswick R, Kirwan M, Dokal I. TINF2 mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosis congenita and related bone marrow failure syndromes. Blood. 2008;112:3594-600 pubmed publisher
    b>Dyskeratosis congenita (DC) is a multisystem bone marrow failure syndrome characterized by a triad of mucocutaneous abnormalities and a predisposition to cancer. The genetic basis of DC remains unknown in more than 60% of patients...
  52. Walne A, Dokal I. Advances in the understanding of dyskeratosis congenita. Br J Haematol. 2009;145:164-72 pubmed publisher
    b>Dyskeratosis congenita (DC) is a rare inherited syndrome exhibiting marked clinical and genetic heterogeneity. It is characterised by mucocutaneous abnormalities, bone marrow failure and a predisposition to cancer...
  53. Gu B, Fan J, Bessler M, Mason P. Accelerated hematopoietic stem cell aging in a mouse model of dyskeratosis congenita responds to antioxidant treatment. Aging Cell. 2011;10:338-48 pubmed publisher
    Mutations in DKC1, encoding telomerase associated protein dyskerin, cause X-linked dyskeratosis congenita (DC), a bone marrow (BM) failure, and cancer susceptibility syndrome...