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Blood, 1 September 2007, Vol. 110, No. 5, pp. 1439-1447. Prepublished online as a Blood First Edition Paper on April 27, 2007; DOI 10.1182/blood-2007-02-075598. This Article Full Text Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: blood-2007-02-075598v1 110/5/1439    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Alter, B. P. Articles by Lansdorp, P. M. Search for Related Content PubMed PubMed Citation Articles by Alter, B. P. Articles by Lansdorp, P. M. Related Collections Hematopoiesis and Stem Cells Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Very short telomere length by flow fluorescence in situ hybridization identifies patients with dyskeratosis congenita Blanche P. Alter1, Gabriela M. Baerlocher2, Sharon A. Savage1, Stephen J. Chanock3, Babette B. Weksler4, Judith P. Willner5, June A. Peters1, Neelam Giri1, and Peter M. Lansdorp6 1 Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD; 2 Hematology, University Hospital, Berne, Switzerland; 3 Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD; 4 Department of Medicine, Weill Medical College, New York, NY; 5 Department of Genetics, Mount Sinai School of Medicine, New York, NY; 6 Terry Fox Laboratory, British Columbia Cancer Research Center, Vancouver, Canada 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. We used multicolor flow fluorescence in situ hybridization analysis of median telomere length in total blood leukocytes, granulocytes, lymphocytes, and several lymphocyte subsets to confirm the diagnosis of DC, distinguish patients with DC from unaffected family members, identify clinically silent DC carriers, and discriminate between patients with DC and those with other bone marrow failure disorders. We defined "very short" telomeres as below the first percentile measured among 400 healthy control subjects over the entire age range. Diagnostic sensitivity and specificity of very short telomeres for DC were more than 90% for total lymphocytes, CD45RA+/CD20– naive T cells, and CD20+ B cells. Granulocyte and total leukocyte assays were not specific; CD45RA– memory T cells and CD57+ NK/NKT were not sensitive. We observed very short telomeres in a clinically normal family member who subsequently developed DC. We propose adding leukocyte subset flow fluorescence in situ hybridization telomere length measurement to the evaluation of patients and families suspected to have DC, because the correct diagnosis will substantially affect patient management. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. M. Baerlocher, A. Rovo, A. Muller, S. Matthey, M. Stern, J. Halter, D. Heim, J. Rischewski, A. Gratwohl, and A. Tichelli Cellular senescence of white blood cells in very long-term survivors after allogeneic hematopoietic stem cell transplantation: the role of chronic graft-versus-host disease and female donor sex Blood, July 2, 2009; 114(1): 219 - 222. [Abstract] [Full Text] [PDF] K. E. Nichols and M. Bessler Cancer & inherited bone marrow failure states Blood, June 25, 2009; 113(26): 6502 - 6503. [Full Text] [PDF] B. P. Alter, N. Giri, S. A. Savage, and P. S. 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Hockemeyer, W. Palm, R. C. Wang, S. S. Couto, and T. de Lange Engineered telomere degradation models dyskeratosis congenita Genes & Dev., July 1, 2008; 22(13): 1773 - 1785. [Abstract] [Full Text] [PDF] R. T. Calado and N. S. Young Telomere maintenance and human bone marrow failure Blood, May 1, 2008; 111(9): 4446 - 4455. [Abstract] [Full Text] [PDF] F. D. Goldman, G. Aubert, A. J. Klingelhutz, M. Hills, S. R. Cooper, W. S. Hamilton, A. J. Schlueter, K. Lambie, C. J. Eaves, and P. M. Lansdorp Characterization of primitive hematopoietic cells from patients with dyskeratosis congenita Blood, May 1, 2008; 111(9): 4523 - 4531. [Abstract] [Full Text] [PDF] G. Aubert and P. M. Lansdorp Telomeres and Aging Physiol Rev, April 1, 2008; 88(2): 557 - 579. [Abstract] [Full Text] [PDF] P. M. Lansdorp Telomeres, stem cells, and hematology Blood, February 15, 2008; 111(4): 1759 - 1766. [Abstract] [Full Text] [PDF] B. P. 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