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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 22, 2007 Accepted April 22, 2007 Very short telomere length by flow FISH identifies patients with Dyskeratosis Congenita Blanche P. Alter*, Gabriela M. Baerlocher, Sharon A. Savage, Stephen J. Chanock, Babette B. Weksler, Judith P. Willner, June A. Peters, Neelam Giri, and Peter M. Lansdorp Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, NCI, NIH, Dept of Health & Human Services, Bethesda, MD, United States Dept of Hematology, University Hospital, Berne, Switzerland Pediatric Oncology Branch, NCI, Bethesda, MD, United States Dept of Medicine, Weill Medical College, New York, NY, United States Dept of Genetics, Mount Sinai School of Medicine, New York, NY, United States Terry Fox Laboratory, British Columbia Cancer Research Center, Vancouver, BC, Canada * Corresponding author; email: alterb{at}mail.nih.gov. 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; DC patients have very short telomeres. We used multicolor flow FISH analysis of median telomere length in total blood leukocytes, granulocytes, lymphocytes, and several lymphocyte subsets to: confirm the diagnosis of DC, distinguish DC patients from unaffected family members, identify clinically silent DC carriers, and discriminate between DC patients and those with other bone marrow failure disorders. We defined "very short" telomeres as below the 1st percentile measured among 400 normal controls over the entire age range. Diagnostic sensitivity and specificity of very short telomeres for DC were >90% for total lymphocytes, CD45RA-positive/CD20-negative naive T-cells, and CD20-positive B-cells. Granulocyte and total leukocyte assays were not specific; CD45RA-negative memory T-cells and CD57-positive 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 FISH telomere length measurement to the evaluation of patients and families suspected to have DC, since 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. Rosenberg Cancer in dyskeratosis congenita Blood, June 25, 2009; 113(26): 6549 - 6557. [Abstract] [Full Text] [PDF] H.-Y. Du, E. Pumbo, J. Ivanovich, P. An, R. T. Maziarz, U. M. Reiss, D. Chirnomas, A. Shimamura, A. Vlachos, J. M. Lipton, et al. TERC and TERT gene mutations in patients with bone marrow failure and the significance of telomere length measurements Blood, January 8, 2009; 113(2): 309 - 316. [Abstract] [Full Text] [PDF] B. P. Alter, G. Baerlocher, N. Giri, P. M. Lansdorp, and S. A Savage Very Short Telomeres Are Characteristic of Dyskeratosis Congenita and Not Other Inherited Bone Marrow Failure Syndromes Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 1044 - 1044. [Abstract] J. K. Alder, J. J.-L. Chen, L. Lancaster, S. Danoff, S.-c. Su, J. D. Cogan, I. Vulto, M. Xie, X. Qi, R. M. Tuder, et al. Short telomeres are a risk factor for idiopathic pulmonary fibrosis PNAS, September 2, 2008; 105(35): 13051 - 13056. [Abstract] [Full Text] [PDF] D. 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. 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