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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2680-2685. Prepublished online as a Blood First Edition Paper on December 6, 2005; DOI 10.1182/blood-2005-07-2622. This Article Full Text (PDF) All Versions of this Article: 2005-07-2622v1 107/7/2680    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Vulliamy, T. J Articles by Dokal, I. Search for Related Content PubMed PubMed Citation Articles by Vulliamy, T. J Articles by Dokal, I. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 1, 2005 Accepted November 20, 2005 Mutations in dyskeratosis congenita: their impact on telomere length and the diversity of clinical presentation Tom J Vulliamy*, Anna Marrone, Stuart W Knight, Amanda Walne, Philip J Mason, and Inderjeet Dokal Department of Hematology, Division of Investigative Science, Imperial College London, Hammersmith Hospital, London, United Kingdom * Corresponding author; email: t.vulliamy{at}imperial.ac.uk. 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. In reviewing the mutation profile that is found in DC we describe 9 novel mutations in the DKC1 gene and 3 novel TERC mutations, responsible for the X-linked and autosomal dominant forms of the disease respectively, but find that two thirds of the families do not have mutations in either of these genes. In a significant subset of these uncharacterised families, the index case presents with severe disease previously defined as the Hoyeraal-Hreidarsson (HH) syndrome. The diverse clinical phenotype seen in patients with X-linked DC is not explained by the different amino acid substitutions: presentation of the recurrent A353V substitution ranges from classical DC to the severe HH variant. However, we do see that patients with HH have significantly shorter telomeres than those with a relatively mild presentation. In the new families described with TERC mutations, there is further evidence of disease anticipation associated with shorter telomeres in the younger generations. This study highlights the considerable genetic and phenotypic diversity of DC. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. P. Alter, N. Giri, S. A. Savage, and P. S. Rosenberg Cancer in dyskeratosis congenita Blood, June 25, 2009; 113(26): 6549 - 6557. [Abstract] [Full Text] [PDF] J. Lee, R. Reddy, L. Barsky, J. Scholes, H. Chen, W. Shi, and B. Driscoll Lung alveolar integrity is compromised by telomere shortening in telomerase-null mice Am J Physiol Lung Cell Mol Physiol, January 1, 2009; 296(1): L57 - L70. [Abstract] [Full Text] [PDF] A. J. Walne, T. Vulliamy, R. Beswick, M. Kirwan, and I. Dokal TINF2 mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosis congenita and related bone marrow failure syndromes Blood, November 1, 2008; 112(9): 3594 - 3600. [Abstract] [Full Text] [PDF] T. M. Errington, D. Fu, J. M. Y. Wong, and K. 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