Mutations of telomerase complex genes linked to bone marrow failures.
Mutations of telomerase complex genes linked to bone marrow failures.
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DOI：
10.1272/jnms.74.202
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发表时间：
2007-06
期刊：
影响因子：
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通讯作者：
H. Yamaguchi
中科院分区：
文献类型：
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作者：
H. Yamaguchi
先天性角化不良（DKC）是一种骨髓衰竭（BMF），具有特征性的身体异常，通常在儿童时期诊断。已知某些形式的DKC是由DKC1、端粒酶RNA组分（TERC）和端粒酶逆转录酶（TERT）发生突变引起的。这些基因是端粒酶复合物的主要成分，在复制端粒和稳定它们防止缩短方面发挥作用。这些基因的突变可以缩短端粒，损害造血干细胞的增殖能力，最终导致DKC。最近，在一些再生障碍性贫血（AA）和骨髓增生异常综合征（MDS）病例中报道了TERC和TERT的突变。这些病例被认为是DKC的非典型形式，在成年期发展缓慢，没有特征性的身体异常。基因检测是诊断这种晚期DKC和确定适当治疗的必要条件。本文综述了端粒酶复合物的突变及其与DKC和骨髓衰竭的关系。
Dyskeratosis congenita (DKC) is a bone marrow failure (BMF) with characteristic physical anomalies, and is typically diagnosed in childhood. Some forms of DKC are known to be caused by mutations occurring in DKC1, telomerase RNA component (TERC), and telomerase reverse transcriptase (TERT). These genes are the main constituents of the telomerase complex that plays a role in replicating telomeres and stabilizing them against shortening. Mutations in these genes could shorten telomeres and impair the proliferative capacity of hematopoietic stem cells, eventually causing DKC. Recently, mutations in TERC and TERT have been reported in some cases of aplastic anemia (AA) and myelodysplastic syndrome (MDS). These cases are considered to be atypical forms of DKC that develop slowly in adulthood without characteristic physical anomalies. Genetic tests are essential in diagnosing this late-presenting DKC and determining the appropriate treatment. This article reviews mutations in the telomerase complex and their connections with DKC and bone marrow failures.