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Nucleic Acids Research Advance Access first published online on October 2, 2007
This version published online on October 3, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm644
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© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Human diseases of telomerase dysfunction: insights into tissue aging

Christine Kim Garcia1, Woodring E. Wright2 and Jerry W. Shay2,*

1McDermott Center for Human Growth and Development and the Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine and 2Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA

*To whom correspondence should be addressed. Tel: +1 214-648-3282; Fax: +1 214-648-8694; Email: jerry.shay{at}utsouthwestern.edu

Received June 29, 2007. Revised August 2, 2007. Accepted August 2, 2007.

There are at least three human diseases that are associated with germ-line mutations of the genes encoding the two essential components of telomerase, TERT and TERC. Heterozygous mutations of these genes have been described for patients with dyskeratosis congenita, bone marrow failure and idiopathic pulmonary fibrosis. In this review, we will detail the clinical similarities and difference of these diseases and review the molecular phenotypes observed. The spectrum of mutations in TERT and TERC varies for these diseases and may in part explain the clinical differences observed. Environmental insults and genetic modifiers that accelerate telomere shortening and increase cell turnover may exaggerate the effects of telomerase haploinsufficiency, contributing to the variability of age of onset as well as tissue-specific organ pathology. A central still unanswered question is whether telomerase dysfunction and short telomeres are a much more prominent factor than previously suspected in other adult-onset, age-related diseases. Understanding the biological effects of these mutations may ultimately lead to novel treatments for these patients.


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