Very short telomere length by flow fluorescence in situ hybridization 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, Peter M. Lansdorp

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1439-1447
Number of pages9
JournalBlood
Volume110
Issue number5
DOIs
StatePublished - Sep 1 2007
Externally publishedYes

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Dyskeratosis Congenita
Lymphocytes
Telomere
Fluorescence In Situ Hybridization
T-cells
Fluorescence
Bone
Assays
Leukocytes
Blood
Genes
Cells
Granulocytes
Data storage equipment
T-Lymphocytes
Lymphocyte Subsets
Healthy Volunteers
B-Lymphocytes
Bone Marrow
Maintenance

ASJC Scopus subject areas

  • Hematology

Cite this

Alter, B. P., Baerlocher, G. M., Savage, S. A., Chanock, S. J., Weksler, B. B., Willner, J. P., ... Lansdorp, P. M. (2007). Very short telomere length by flow fluorescence in situ hybridization identifies patients with dyskeratosis congenita. Blood, 110(5), 1439-1447. https://doi.org/10.1182/blood-2007-02-075598

Very short telomere length by flow fluorescence in situ hybridization identifies patients with dyskeratosis congenita. / Alter, Blanche P.; Baerlocher, Gabriela M.; Savage, Sharon A.; Chanock, Stephen J.; Weksler, Babette B.; Willner, Judith P.; Peters, June A.; Giri, Neelam; Lansdorp, Peter M.

In: Blood, Vol. 110, No. 5, 01.09.2007, p. 1439-1447.

Research output: Contribution to journalArticle

Alter, BP, Baerlocher, GM, Savage, SA, Chanock, SJ, Weksler, BB, Willner, JP, Peters, JA, Giri, N & Lansdorp, PM 2007, 'Very short telomere length by flow fluorescence in situ hybridization identifies patients with dyskeratosis congenita', Blood, vol. 110, no. 5, pp. 1439-1447. https://doi.org/10.1182/blood-2007-02-075598
Alter BP, Baerlocher GM, Savage SA, Chanock SJ, Weksler BB, Willner JP et al. Very short telomere length by flow fluorescence in situ hybridization identifies patients with dyskeratosis congenita. Blood. 2007 Sep 1;110(5):1439-1447. https://doi.org/10.1182/blood-2007-02-075598
Alter, Blanche P. ; Baerlocher, Gabriela M. ; Savage, Sharon A. ; Chanock, Stephen J. ; Weksler, Babette B. ; Willner, Judith P. ; Peters, June A. ; Giri, Neelam ; Lansdorp, Peter M. / Very short telomere length by flow fluorescence in situ hybridization identifies patients with dyskeratosis congenita. In: Blood. 2007 ; Vol. 110, No. 5. pp. 1439-1447.
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