Human diseases of telomerase dysfunction: Insights into tissue aging

Christine Kim Garcia, Woodring E. Wright, Jerry W. Shay

Research output: Contribution to journalReview articlepeer-review

124 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)7406-7416
Number of pages11
JournalNucleic acids research
Issue number22
StatePublished - Dec 2007

ASJC Scopus subject areas

  • Genetics


Dive into the research topics of 'Human diseases of telomerase dysfunction: Insights into tissue aging'. Together they form a unique fingerprint.

Cite this