Advances in the understanding of dyskeratosis congenita
Open Access
- 26 March 2009
- journal article
- review article
- Published by Wiley in British Journal of Haematology
- Vol. 145 (2), 164-172
- https://doi.org/10.1111/j.1365-2141.2009.07598.x
Abstract
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. Bone marrow failure is the principal cause of premature mortality. Studies over the last 10 years have demonstrated that DC is principally a disease of defective telomere maintenance. All DC patients have very short telomeres and the genetically characterised cases of DC have mutations in six genes which either encode components of the telomerase complex (DKC1, TERC, TERT, NOP10, NHP2) or shelterin (TINF2); these are important in the elongation and protection of the telomeric end, respectively. These advances have led to the recognition of cryptic forms of DC, such as presentations with aplastic anaemia and myelodysplasia. They have also increased our understanding of normal haematopoiesis and provided new insights to the aetiology of some cases of aplastic anaemia and related haematological disorders.Keywords
This publication has 68 references indexed in Scilit:
- A pathogenic dyskerin mutation impairs proliferation and activates a DNA damage response independent of telomere length in miceProceedings of the National Academy of Sciences of the United States of America, 2008
- Engineered telomere degradation models dyskeratosis congenitaGenes & Development, 2008
- Mutations in the telomerase component NHP2 cause the premature ageing syndrome dyskeratosis congenitaProceedings of the National Academy of Sciences of the United States of America, 2008
- The role of telomere biology in bone marrow failure and other disordersMechanisms of Ageing and Development, 2008
- TINF2, a Component of the Shelterin Telomere Protection Complex, Is Mutated in Dyskeratosis CongenitaAmerican Journal of Human Genetics, 2008
- The Telomerase DatabaseNucleic Acids Research, 2007
- Genetic heterogeneity in autosomal recessive dyskeratosis congenita with one subtype due to mutations in the telomerase-associated protein NOP10Human Molecular Genetics, 2007
- Adult-onset pulmonary fibrosis caused by mutations in telomeraseProceedings of the National Academy of Sciences, 2007
- A critical role for TPP1 and TIN2 interaction in high-order telomeric complex assemblyProceedings of the National Academy of Sciences of the United States of America, 2006
- Disease states associated with telomerase deficiency appear earlier in mice with short telomeresThe EMBO Journal, 1999