Blood Journal
Leading the way in experimental and clinical research in hematology

Very short telomere length by flow fluorescence in situ hybridization identifies patients with dyskeratosis congenita

  1. Blanche P. Alter1,
  2. Gabriela M. Baerlocher2,
  3. Sharon A. Savage1,
  4. Stephen J. Chanock3,
  5. Babette B. Weksler4,
  6. Judith P. Willner5,
  7. June A. Peters1,
  8. Neelam Giri1, and
  9. Peter M. Lansdorp6
  1. 1Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD;
  2. 2Hematology, University Hospital, Berne, Switzerland;
  3. 3Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD;
  4. 4Department of Medicine, Weill Medical College, New York, NY;
  5. 5Department of Genetics, Mount Sinai School of Medicine, New York, NY;
  6. 6Terry Fox Laboratory, British Columbia Cancer Research Center, Vancouver, Canada
  1. Presented in abstract form at the 48th annual meeting of the American Society of Hematology, Orlando, FL, December 11, 2006 (Abstract 183).


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.

  • Submitted February 22, 2007.
  • Accepted April 22, 2007.
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