Journal article

Inherited bone marrow failure associated with germline mutation of ACD, the gene encoding telomere protein TPP1

Yiran Guo, Melissa Kartawinata, Jiankang Li, Hilda A Pickett, Juliana Teo, Tatjana Kilo, Pasquale M Barbaro, Brendan Keating, Yulan Chen, Lifeng Tian, Ahmad Al-Odaib, Roger R Reddel, John Christodoulou, Xun Xu, Hakon Hakonarson, Tracy M Bryan

BLOOD | AMER SOC HEMATOLOGY | Published : 2014


Telomerase is a ribonucleoprotein enzyme that is necessary for overcoming telomere shortening in human germ and stem cells. Mutations in telomerase or other telomere-maintenance proteins can lead to diseases characterized by depletion of hematopoietic stem cells and bone marrow failure (BMF). Telomerase localization to telomeres requires an interaction with a region on the surface of the telomere-binding protein TPP1 known as the TEL patch. Here, we identify a family with aplastic anemia and other related hematopoietic disorders in which a 1-amino-acid deletion in the TEL patch of TPP1 (ΔK170) segregates with disease. All family members carrying this mutation, but not those with wild-type TP..

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Awarded by Cancer Council NSW

Funding Acknowledgements

This work was supported by an Institutional Development Award to the Center for Applied Genomics from The Children's Hospital of Philadelphia, an Australian Awards Scholarship (M.K.), a Cancer Institute New South Wales (NSW) Career Development Fellowship (H.A.P.), a scholarship to A.A.-O. provided by the Academic and Training Affairs at King Faisal Specialist Hospital and Research Center and the Ministry of Higher Education (Riyadh, Saudi Arabia), project support from the Kids Cancer Alliance (NSW), a National Health and Medical Research Council postgraduate medical/dental scholarship (P.M.B.), program grant PG11-08 from Cancer Council NSW (R.R.), and a Cancer Institute NSW Career Development and Support Fellowship and project grant RG10-02 from Cancer Council NSW (T.M.B).