Functional characterization of telomerase RNA variants found in patients with hematologic disorders

Hinh Ly, Rodrigo T. Calado, Paulette Allard, Gabriela M. Baerlocher, Peter M. Lansdorp, Neal S. Young, Tristram G. Parslow

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


Human telomerase uses a specific cellular RNA, called hTERC, as the template to synthesize telomere repeats at chromosome ends. Approximately 10% to 15% of patients with aplastic anemia or other bone marrow failure syndromes are carriers of hTERC sequence variants whose functional significance, in most cases, is unknown. We screened 10 reported and 2 newly discovered hTERC variants from such patients and found that 10 of these negatively affected telomerase enzymatic function when they were used to reconstitute telomerase enzymatic function in human cells. Most functional deficits were due to perturbations of hTERC secondary structure and correlated well with the degrees of telomere shortening and reduced telomerase activity observed in peripheral blood lymphocytes of the representative patients. We also found no evidence of dominant-negative activity in any of the mutants. Therefore, loss of telomerase activity and of telomere maintenance resulting from inherited hTERC mutations may limit marrow stem cell renewal and predispose some patients to bone marrow failure.

Original languageEnglish (US)
Pages (from-to)2332-2339
Number of pages8
Issue number6
StatePublished - Mar 15 2005


Dive into the research topics of 'Functional characterization of telomerase RNA variants found in patients with hematologic disorders'. Together they form a unique fingerprint.

Cite this