Open Access Open Badges Case report

A mutation in the H/ACA box of telomerase RNA component gene (TERC) in a young patient with myelodysplastic syndrome

Yasutaka Ueda1*, Rodrigo T Calado2, Anna Norberg3, Sachiko Kajigaya1, Göran Roos4, Eva Hellstrom-Lindberg5 and Neal S Young1

Author Affiliations

1 Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bldg 10-CRC, Rm 3E-5216, 9000 Rockville Pike, Bethesda, MD 20892, USA

2 Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil

3 Department of Medical Biosciences, Medical and Clinical Genetics, Umeå University, Umeå, Sweden

4 Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden

5 Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden

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BMC Medical Genetics 2014, 15:68  doi:10.1186/1471-2350-15-68

Published: 19 June 2014



Telomeres are repeated sequences (the hexanucleotide TTAGGG in vertebrates) located at chromosome ends of eukaryotes, protecting DNA from end joining or degradation. Telomeres become shorter with each cell cycle, but telomerase, a ribonucleoprotein complex, alleviates this attrition. The telomerase RNA component (TERC) is an essential element of telomerase, serving as a template for telomere elongation. The H/ACA domain of TERC is indispensable for telomere biogenesis. Mutations in the telomerase components allow accelerated telomere loss, resulting in various disease manifestations, including bone marrow failure. To date, this is the first detailed report of an H-box mutation in TERC that is related to human disease.

Case presentation

A 26-year-old man with myelodysplastic syndrome (MDS) had very short telomeres. Sequencing identified a single heterozygous mutation in the H box of the patient’s TERC gene. The same mutation was also present in his father and his son, demonstrating that it was germline in origin. The telomere length in the father’s blood was shorter compared to age-matched healthy controls, while it was normal in the son and also in the sperm cells of the patient. In vitro experiments suggested that the mutation was responsible for the telomere shortening in the patient’s leukocytes and contributed to the pathogenesis of bone marrow failure in our patient.


We analyzed a mutation (A377G) in the H box of TERC in a young MDS patient who had significantly short-for-age telomeres. As telomeres protect chromosomes from instability, it is highly plausible that this genetic lesion was responsible for the patient’s hematological manifestations, including marrow failure and aneuploidy in the hematopoietic stem cell compartment.

Myelodysplastic syndrome (MDS); Telomerase RNA component (TERC); H/ACA box; Southern blotting; Single Telomere Elongation Length Analysis (STELA); RNA fluorescence in situ hybridization (RNA FISH)