Encyclopedia of Medical Immunology

Living Edition
| Editors: Ian MacKay, Noel R. Rose

DKC1, Dyskeratosis Congenita/Hoyeraal-Hreidarsson Syndrome

  • Nicholas L. RiderEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-9209-2_209-1


DKC1 encodes the dyskerin protein, a member of the human telomerase complex (Mochizuki et al. 2004). The gene is comprised by 15 exons spanning approximately 16 kb, located at Xq28 (Hassock et al. 1999). Human telomerase is a ribonucleoprotein complex which functions to maintain telomere length during normal cell division through controlled elongation thereby preventing shortening and ensuing cell cycle arrest and cell death (Du et al. 2009). Hemizygous pathogenic variants in DKC1 lead to dyskeratosis congenita and the Hoyeraal-Hreidarsson syndrome (Knight et al. 1999a, b).

Clinical Relevance

Defects of human telomerase biology lead principally to dyskeratosis congenita (DC) (Mitchell et al. 1999). Patients with DC often present with progressive bone marrow failure and a triad of mucocutaneous findings which includes abnormal skin pigmentation, dystrophic nails, and leukoplakia of the oral mucosa (Dokal 2000). It is important to note that a minority of DC patients present...

This is a preview of subscription content, log in to check access.


  1. Alter BP, Rosenberg PS, Giri N, Baerlocher GM, Lansdorp PM, Savage SA. Telomere length is associated with disease severity and declines with age in dyskeratosis congenita. Haematologica. 2012;97(3):353–9.CrossRefGoogle Scholar
  2. Aubert G, Hills M, Lansdorp PM. Telomere length measurement-caveats and a critical assessment of the available technologies and tools. Mutat Res. 2012;730(1–2):59–67.CrossRefGoogle Scholar
  3. Dietz AC, Orchard PJ, Baker KS, et al. Disease-specific hematopoietic cell transplantation: nonmyeloablative conditioning regimen for dyskeratosis congenita. Bone Marrow Transplant. 2011;46(1):98–104.CrossRefGoogle Scholar
  4. Dokal I. Dyskeratosis congenita in all its forms. Br J Haematol. 2000;110(4):768–79.CrossRefGoogle Scholar
  5. Du HY, Pumbo E, Ivanovich J, et al. TERC and TERT gene mutations in patients with bone marrow failure and the significance of telomere length measurements. Blood. 2009;113(2):309–16.CrossRefGoogle Scholar
  6. Hassock S, Vetrie D, Giannelli F. Mapping and characterization of the X-linked dyskeratosis congenita (DKC) gene. Genomics. 1999;55(1):21–7.CrossRefGoogle Scholar
  7. Houben JM, Moonen HJ, van Schooten FJ, Hageman GJ. Telomere length assessment: biomarker of chronic oxidative stress? Free Radic Biol Med. 2008;44(3):235–46.CrossRefGoogle Scholar
  8. Khincha PP, Savage SA. Neonatal manifestations of inherited bone marrow failure syndromes. Semin Fetal Neonatal Med. 2016;21(1):57–65.CrossRefGoogle Scholar
  9. Knight SW, Heiss NS, Vulliamy TJ, et al. Unexplained aplastic anaemia, immunodeficiency, and cerebellar hypoplasia (Hoyeraal-Hreidarsson syndrome) due to mutations in the dyskeratosis congenita gene, DKC1. Br J Haematol. 1999a;107(2):335–9.CrossRefGoogle Scholar
  10. Knight SW, Heiss NS, Vulliamy TJ, et al. X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene. Am J Hum Genet. 1999b;65(1):50–8.CrossRefGoogle Scholar
  11. Mitchell JR, Wood E, Collins K. A telomerase component is defective in the human disease dyskeratosis congenita. Nature. 1999;402(6761):551–5.CrossRefGoogle Scholar
  12. Mochizuki Y, He J, Kulkarni S, Bessler M, Mason PJ. Mouse dyskerin mutations affect accumulation of telomerase RNA and small nucleolar RNA, telomerase activity, and ribosomal RNA processing. Proc Natl Acad Sci U S A. 2004;101(29):10756–61.CrossRefGoogle Scholar
  13. Shimamura A, Alter BP. Pathophysiology and management of inherited bone marrow failure syndromes. Blood Rev. 2010;24(3):101–22.CrossRefGoogle Scholar
  14. Townsley DM, Dumitriu B, Young NS. Bone marrow failure and the telomeropathies. Blood. 2014;124(18):2775–83.CrossRefGoogle Scholar
  15. Townsley DM, Dumitriu B, Liu D, et al. Danazol treatment for telomere diseases. N Engl J Med. 2016;374(20):1922–31.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Section of Immunology, Allergy and Retrovirology, Department of Pediatrics, Baylor College of MedicineTexas Children’s HospitalHoustonUSA

Section editors and affiliations

  • Javier Chinen
    • 1
  1. 1.Division of Allergy and Immunology, Department of PediatricsBaylor College of Medicine, Texas Children’s HospitalThe WoodlandsUSA