Human diseases of telomerase dysfunction: insights into tissue aging.
Human diseases of telomerase dysfunction: insights into tissue aging.
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DOI：
10.1093/nar/gkm644
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发表时间：
2007
影响因子：
14.9
通讯作者：
Shay, Jerry W
中科院分区：
文献类型：
--
作者：
Garcia, Christine Kim;Wright, Woodring E;Shay, Jerry W
至少有三种人类疾病与编码端粒酶两个基本成分TERT和TERC的基因胚系突变有关。这些基因的杂合突变已被描述为先天性角化不良、骨髓衰竭和特发性肺纤维化的患者。在这篇综述中，我们将详细介绍这些疾病的临床相似性和差异性，并回顾观察到的分子表型。TERT和TERC的突变谱因这些疾病而异，这可能部分解释了观察到的临床差异。环境侮辱和遗传修饰物加速端粒缩短和增加细胞周转可能会夸大端粒酶单倍体不足的影响，导致发病年龄和组织特异性器官病理的变异性。一个中心仍未回答的问题是，在其他成人发病的年龄相关疾病中，端粒酶功能障碍和端粒缩短是否是比之前怀疑的更突出的因素。了解这些突变的生物学效应最终可能会为这些患者带来新的治疗方法。
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.