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Human diseases of telomerase dysfunction: insights into tissue aging
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...
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
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Oxford University Press
2007
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190725/ https://www.ncbi.nlm.nih.gov/pubmed/17913752 http://dx.doi.org/10.1093/nar/gkm644 |
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author | Garcia, Christine Kim Wright, Woodring E. Shay, Jerry W. |
author_facet | Garcia, Christine Kim Wright, Woodring E. Shay, Jerry W. |
author_sort | Garcia, Christine Kim |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2190725 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21907252008-01-25 Human diseases of telomerase dysfunction: insights into tissue aging Garcia, Christine Kim Wright, Woodring E. Shay, Jerry W. Nucleic Acids Res Survey and Summary 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. Oxford University Press 2007-12 2007-10-02 /pmc/articles/PMC2190725/ /pubmed/17913752 http://dx.doi.org/10.1093/nar/gkm644 Text en © 2007 The Author(s) http://creativecommons.org/licenses/by-nc/2.0/uk/ 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. |
spellingShingle | Survey and Summary Garcia, Christine Kim Wright, Woodring E. Shay, Jerry W. Human diseases of telomerase dysfunction: insights into tissue aging |
title | Human diseases of telomerase dysfunction: insights into tissue aging |
title_full | Human diseases of telomerase dysfunction: insights into tissue aging |
title_fullStr | Human diseases of telomerase dysfunction: insights into tissue aging |
title_full_unstemmed | Human diseases of telomerase dysfunction: insights into tissue aging |
title_short | Human diseases of telomerase dysfunction: insights into tissue aging |
title_sort | human diseases of telomerase dysfunction: insights into tissue aging |
topic | Survey and Summary |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190725/ https://www.ncbi.nlm.nih.gov/pubmed/17913752 http://dx.doi.org/10.1093/nar/gkm644 |
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