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

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

  1. Hong-Yan Du1,
  2. Elena Pumbo1,
  3. Jennifer Ivanovich2,
  4. Ping An3,
  5. Richard T. Maziarz4,
  6. Ulrike M. Reiss5,
  7. Deborah Chirnomas6,
  8. Akiko Shimamura6,
  9. Adrianna Vlachos7,
  10. Jeffrey M. Lipton7,
  11. Rakesh K. Goyal8,
  12. Frederick Goldman9,
  13. David B. Wilson10,
  14. Philip J. Mason1, and
  15. Monica Bessler1
  1. Departments of 1Internal Medicine
  2. 2Surgery, and
  3. 3Genetics, Washington University School of Medicine, St Louis, MO;
  4. 4Division of Hematology, Oregon Health & Science University, Portland;
  5. 5St Jude Children's Research Hospital, Memphis, TN;
  6. 6Department of Hematology, Children's Hospital Boston, MA;
  7. 7The Feinstein Institute for Medical Research, Schneider Children's Hospital, Albert Einstein College of Medicine, New Hyde Park, NY;
  8. 8Department of Pediatrics, Children's Hospital of Pittsburgh, PA;
  9. 9Department of Pediatrics, University of Iowa Children's Hospital, Iowa City; and
  10. 10Department of Pediatrics, Washington University School of Medicine, St Louis, MO


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 TERT gene 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 of telomere length is a sensitive but nonspecific screening method for DC. In the absence of BMF, telomere length measurements should be interpreted with caution.

  • Submitted July 3, 2008.
  • Accepted September 21, 2008.
View Full Text