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Blood, 15 August 2005, Vol. 106, No. 4, pp. 1246-1252. Prepublished online as a Blood First Edition Paper on May 10, 2005; DOI 10.1182/blood-2005-01-0247. This Article Full Text (PDF) All Versions of this Article: 2005-01-0247v1 106/4/1246    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 Ly, H. Articles by Lansdorp, P. M Search for Related Content PubMed PubMed Citation Articles by Ly, H. Articles by Lansdorp, P. M Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 19, 2005 Accepted April 16, 2005 Identification and functional characterization of two variant alleles of the telomerase RNA template gene (TERC) in a patient with Dyskeratosis Congenita Hinh Ly, Mike Schertzer, Wasil Jastaniah, Jeff Davis, Siu Li Yong, Qin Ouyang, Elizabeth H Blackburn, Tristram G Parslow, and Peter M Lansdorp* Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada Pediatric Hematology-Oncology Group, British Columbia's Children's Hospital, Vancouver, BC, Canada Department of Medical Genetics, Children & Women's Hospital Health Care Centre of BC, University of British Columbia, Vancouver, BC, Canada Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada; Department of Medicine, University of British Columbia, Vancouver, BC, Canada * Corresponding author; email: plansdor{at}bccrc.ca. Heterozygous mutations of the human telomerase RNA template gene (TERC) have been described in patients with acquired aplastic anemia and the autosomal dominant form of Dyskeratosis Congenita (DKC). Patients with mutations in both TERC alleles have not yet been reported. Here, we report a DKC patient who inherited two distinct TERC sequence variants from her parents; a deletion (del-216-229) in one and a point mutation (A37G) in the other allele of the TERC gene. Her marrow was hypocellular and showed an abnormal clone (46, XX t(7;21)(q34;q22). The telomere lengths in leukocytes of the patient and her relatives were shorter than those of the age-matched controls and were progressively shorter in subsequent generations of family members with the del-216-229 allele. Telomerase enzymatic levels in lymphocytes from the patient were approximately half of those measured in normal controls. The del216-229 mutation failed to reconstitute telomerase activity in transfected cells but when co-expressed with the A37G variant telomerase activity was only modestly suppressed. These clinical and laboratory findings support the concept that telomerase levels in human hematopoietic stem cells are tightly controlled as even moderately reduced levels result in accelerated telomere shortening and eventual marrow failure. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. D. Mozdy, E. R. Podell, and T. R. Cech Multiple Yeast Genes, Including Paf1 Complex Genes, Affect Telomere Length via Telomerase RNA Abundance Mol. Cell. Biol., June 15, 2008; 28(12): 4152 - 4161. [Abstract] [Full Text] [PDF] T. Vulliamy, R. Beswick, M. Kirwan, A. Marrone, M. Digweed, A. Walne, and I. 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