Division of Cancer Epidemiology and Genetics, Clinical Genetics Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20892, USA.
Genet Med. 2010 Dec;12(12):753-64. doi: 10.1097/GIM.0b013e3181f415b5.
Telomere biology disorders are a complex set of illnesses defined by the presence of very short telomeres. Individuals with classic dyskeratosis congenita have the most severe phenotype, characterized by the triad of nail dystrophy, abnormal skin pigmentation, and oral leukoplakia. More significantly, these individuals are at very high risk of bone marrow failure, cancer, and pulmonary fibrosis. A mutation in one of six different telomere biology genes can be identified in 50–60% of these individuals. DKC1, TERC, TERT, NOP10, and NHP2 encode components of telomerase or a telomerase-associated factor and TINF2, a telomeric protein. Progressively shorter telomeres are inherited from generation to generation in autosomal dominant dyskeratosis congenita, resulting in disease anticipation. Up to 10% of individuals with apparently acquired aplastic anemia or idiopathic pulmonary fibrosis also have short telomeres and mutations in TERC or TERT. Similar findings have been seen in individuals with liver fibrosis or acute myelogenous leukemia. This report reviews basic aspects of telomere biology and telomere length measurement, and the clinical and genetic features of those disorders that constitute our current understanding of the spectrum of illness caused by defects in telomere biology. We also suggest a grouping schema for the telomere disorders.
端粒生物学障碍是一组由非常短的端粒引起的复杂疾病。经典先天性角化不良患者具有最严重的表型,其特征为三联征:指甲营养不良、皮肤色素异常和口腔白斑。更重要的是,这些个体患骨髓衰竭、癌症和肺纤维化的风险非常高。在这些个体中,有 50-60%可以识别出六种不同的端粒生物学基因中的一个突变。DKC1、TERC、TERT、NOP10 和 NHP2 编码端粒酶或端粒酶相关因子的成分,而 TINF2 则是一种端粒蛋白。常染色体显性先天性角化不良症中,端粒逐渐变短并遗传自一代又一代,导致疾病预期。多达 10%的特发性再生障碍性贫血或特发性肺纤维化患者也具有短端粒和 TERC 或 TERT 的突变。在有肝纤维化或急性髓性白血病的个体中也观察到类似的发现。本报告回顾了端粒生物学和端粒长度测量的基本方面,以及构成我们目前对端粒生物学缺陷引起的疾病谱的理解的那些疾病的临床和遗传特征。我们还建议了端粒疾病的分组方案。
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