TERC and TERT gene mutations in patients with bone marrow failure and the significance of telomere length measurements

Hong Yan Du, Elena Pumbo, Jennifer Ivanovich, Ping An, Richard T. Maziarz, Ulrike M. Reiss, Deborah Chirnomas, Akiko Shimamura, Adrianna Vlachos, Jeffrey M. Lipton, Rakesh K. Goyal, Frederick Goldman, David B. Wilson, Philip J. Mason, Monica Bessler

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Dyskeratosis congenita (DC) is a rare inherited form of bone marrow failure (BMF) caused by mutations in telomere maintaining genes including TERC and TERT. Here we studied the prevalence of TERC and TERT gene mutations and of telomere shortening in an unselected population of patients with BMF at our medical center and in a selected group of patients referred from outside institutions. Less than 5% of patients with BMF had pathogenic mutations in TERC or TERT. In patients with BMF, pathogenic TERC or TERT gene mutations were invariably associated with marked telomere shortening (« 1st percentile) in peripheral blood mononuclear cells (PBMCs). In asymptomatic family members, however, telomere length was not a reliable predictor for the presence or absence of a TERC or TERTgene mutation. Telomere shortening was not pathognomonic of DC, as approximately 30% of patients with BMF due to other causes had PBMC telomere lengths at the 1st percentile or lower. We conclude that in the setting of BMF, measurement oftelomere length is a sensitive but nonspecific screening method for DC. In the absence of BMF, telomere length measurements should be interpreted with caution.

Original languageEnglish (US)
Pages (from-to)309-316
Number of pages8
JournalBlood
Volume113
Issue number2
DOIs
StatePublished - Jan 8 2009

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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