Human Telomere Disease Due to Disruption of the CCAAT Box of the TERC Promoter

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2012 Feb 11

PMID 22323451

Citations 14

Authors

Anna M Aalbers

Sachiko Kajigaya

Marry M van den Heuvel-Eibrink

Vincent H J van der Velden

Rodrigo T Calado

Neal S Young

Affiliations

Soon will be listed here.

Abstract

Mutations in the coding region of telomerase complex genes can result in accelerated telomere attrition and human disease. Manifestations of telomere disease include the bone marrow failure syndromes dyskeratosis congenita and aplastic anemia, acute myeloid leukemia, liver cirrhosis, and pulmonary fibrosis. Here, we describe a mutation in the CCAAT box (GCAAT) of the TERC gene promoter in a family in which multiple members had typical features of telomeropathy. The genetic alteration in this critical regulatory sequence resulted in reduced reporter gene activity and absent binding of transcription factor NF-Y, likely responsible for reduced TERC levels, decreased telomerase activity, and short telomeres. This is the first description of a pathogenic mutation in the highly conserved CCAAT box and the first instance of a mutation in the promoter region of TERC producing a telomeropathy. We propose that current mutation-screening strategies should include gene promoter regions for the diagnosis of telomere diseases. This clinical trial was registered at www.clinicaltrials.gov as #NCT00071045.

Citing Articles

Elevated Telomeric Repeat-Containing RNA (TERRA) Levels Linked to Telomere Dysfunction and Telomerase Inactivity in Blood Cells of Children With Aplastic Anemia.

Mazumdar J, Chowdhury P, Mondal B, Kumar Das A, Ghosh U Cureus. 2024; 16(10):e71241.

PMID: 39525171 PMC: 11550455. DOI: 10.7759/cureus.71241.

TERC haploid cell reprogramming: a novel therapeutic strategy for aplastic anemia.

Tang X, Xu R, Wang Y, Chen K, Cui S Mol Med. 2023; 29(1):94.

PMID: 37424004 PMC: 10332096. DOI: 10.1186/s10020-023-00691-w.

Molecular Mechanisms of Alveolar Epithelial Stem Cell Senescence and Senescence-Associated Differentiation Disorders in Pulmonary Fibrosis.

Hong X, Wang L, Zhang K, Liu J, Liu J Cells. 2022; 11(5).

PMID: 35269498 PMC: 8909789. DOI: 10.3390/cells11050877.

Cancer-associated mutations in the condensin II subunit CAPH2 cause genomic instability through telomere dysfunction and anaphase chromosome bridges.

Weyburne E, Bosco G J Cell Physiol. 2020; 236(5):3579-3598.

PMID: 33078399 PMC: 7983937. DOI: 10.1002/jcp.30113.

Transplantation of a Novel Recombinant Adeno-Associated Virus (pAAV-HE1B19K-TE1A) Demonstrates Higher Anti-Tumor Effects in Tumor Cells.

Li Z, Shen H, Shu K, Li J, Tang Y, Su J Ann Transplant. 2020; 25:e925013.

PMID: 32883945 PMC: 7493455. DOI: 10.12659/AOT.925013.

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