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Telomerase reverse transcriptase haploinsufficiency and telomere length in individuals with 5p– syndrome

Telomerase, which maintains the ends of chromosomes, consists of two core components, the telomerase reverse transcriptase (TERT) and the telomerase RNA (TERC). Haploinsufficiency for TERC or TERT leads to progressive telomere shortening and autosomal dominant dyskeratosis congenita (DC). The clinic...

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Autores principales: Du, Hong-Yan, Idol, Rachel, Robledo, Sara, Ivanovich, Jennifer, An, Ping, Londono-Vallejo, Arturo, Wilson, David B, Mason, Philip J, Bessler, Monica
Formato: Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583393/
https://www.ncbi.nlm.nih.gov/pubmed/17875000
http://dx.doi.org/10.1111/j.1474-9726.2007.00324.x
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author Du, Hong-Yan
Idol, Rachel
Robledo, Sara
Ivanovich, Jennifer
An, Ping
Londono-Vallejo, Arturo
Wilson, David B
Mason, Philip J
Bessler, Monica
author_facet Du, Hong-Yan
Idol, Rachel
Robledo, Sara
Ivanovich, Jennifer
An, Ping
Londono-Vallejo, Arturo
Wilson, David B
Mason, Philip J
Bessler, Monica
author_sort Du, Hong-Yan
collection PubMed
description Telomerase, which maintains the ends of chromosomes, consists of two core components, the telomerase reverse transcriptase (TERT) and the telomerase RNA (TERC). Haploinsufficiency for TERC or TERT leads to progressive telomere shortening and autosomal dominant dyskeratosis congenita (DC). The clinical manifestations of autosomal dominant DC are thought to occur when telomeres become critically short, but the rate of telomere shortening in this condition is unknown. Here, we investigated the consequences of de novo TERT gene deletions in a large cohort of individuals with 5p– syndrome. The study group included 41 individuals in which the chromosome deletion resulted in loss of one copy of the TERT gene at 5p15.33. Telomere length in peripheral blood cells from these individuals, although within the normal range, was on average shorter than in normal controls. The shortening was more significant in older individuals suggesting an accelerated age-dependent shortening. In contrast, individuals with autosomal dominant DC due to an inherited TERC gene deletion had very short telomeres, and the telomeres were equally short regardless of the age. Although some individuals with 5p– syndrome showed clinical features that were reminiscent of autosomal dominant DC, these features did not correlate with telomere length, suggesting that these were not caused by critically short telomeres. We conclude that a TERT gene deletion leads to slightly shorter telomeres within one generation. However, our results suggest that several generations of TERT haploinsufficiency are needed to produce the very short telomeres seen in patients with DC.
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spelling pubmed-25833932008-11-18 Telomerase reverse transcriptase haploinsufficiency and telomere length in individuals with 5p– syndrome Du, Hong-Yan Idol, Rachel Robledo, Sara Ivanovich, Jennifer An, Ping Londono-Vallejo, Arturo Wilson, David B Mason, Philip J Bessler, Monica Aging Cell Original Articles Telomerase, which maintains the ends of chromosomes, consists of two core components, the telomerase reverse transcriptase (TERT) and the telomerase RNA (TERC). Haploinsufficiency for TERC or TERT leads to progressive telomere shortening and autosomal dominant dyskeratosis congenita (DC). The clinical manifestations of autosomal dominant DC are thought to occur when telomeres become critically short, but the rate of telomere shortening in this condition is unknown. Here, we investigated the consequences of de novo TERT gene deletions in a large cohort of individuals with 5p– syndrome. The study group included 41 individuals in which the chromosome deletion resulted in loss of one copy of the TERT gene at 5p15.33. Telomere length in peripheral blood cells from these individuals, although within the normal range, was on average shorter than in normal controls. The shortening was more significant in older individuals suggesting an accelerated age-dependent shortening. In contrast, individuals with autosomal dominant DC due to an inherited TERC gene deletion had very short telomeres, and the telomeres were equally short regardless of the age. Although some individuals with 5p– syndrome showed clinical features that were reminiscent of autosomal dominant DC, these features did not correlate with telomere length, suggesting that these were not caused by critically short telomeres. We conclude that a TERT gene deletion leads to slightly shorter telomeres within one generation. However, our results suggest that several generations of TERT haploinsufficiency are needed to produce the very short telomeres seen in patients with DC. Blackwell Publishing Ltd 2007-10-01 /pmc/articles/PMC2583393/ /pubmed/17875000 http://dx.doi.org/10.1111/j.1474-9726.2007.00324.x Text en © 2007 The Authors Journal compilation © Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland 2007 https://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
spellingShingle Original Articles
Du, Hong-Yan
Idol, Rachel
Robledo, Sara
Ivanovich, Jennifer
An, Ping
Londono-Vallejo, Arturo
Wilson, David B
Mason, Philip J
Bessler, Monica
Telomerase reverse transcriptase haploinsufficiency and telomere length in individuals with 5p– syndrome
title Telomerase reverse transcriptase haploinsufficiency and telomere length in individuals with 5p– syndrome
title_full Telomerase reverse transcriptase haploinsufficiency and telomere length in individuals with 5p– syndrome
title_fullStr Telomerase reverse transcriptase haploinsufficiency and telomere length in individuals with 5p– syndrome
title_full_unstemmed Telomerase reverse transcriptase haploinsufficiency and telomere length in individuals with 5p– syndrome
title_short Telomerase reverse transcriptase haploinsufficiency and telomere length in individuals with 5p– syndrome
title_sort telomerase reverse transcriptase haploinsufficiency and telomere length in individuals with 5p– syndrome
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583393/
https://www.ncbi.nlm.nih.gov/pubmed/17875000
http://dx.doi.org/10.1111/j.1474-9726.2007.00324.x
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