Dyskeratosis Congenita
Dyskeratosis Congenita
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DOI：
10.1182/asheducation-2011.1.480
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发表时间：
2011-12-01
期刊：
影响因子：
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通讯作者：
Dokal, Inderjeet
中科院分区：
文献类型：
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作者：
Dokal, Inderjeet
先天性角化不良（DC）是一种多系统遗传性综合征，表现出显著的临床和遗传异质性。其经典形式的特征是黏膜皮肤异常、骨髓衰竭以及易患癌症。骨髓衰竭是过早死亡的主要原因。过去15年的研究取得了重大进展，已经确定了8个DC基因（DKC1、TERC、TERT、NOP10、NHP2、TIN2、C16orf57和TCAB1）。其中7个基因在端粒维持中起重要作用，要么是因为它们编码端粒酶复合物的成分（DKC1、TERC、TERT、NOP10、NHP2和TCAB1），要么是编码 shelterin复合物（TINF2）。因此，DC主要是一种端粒维持缺陷性疾病，患者通常端粒极短。遗传学的进展使DC与其他几种疾病统一起来，包括严重的多系统疾病霍耶拉尔 - 赫雷达尔松综合征和雷韦斯综合征，以及再生障碍性贫血、骨髓增生异常、白血病和特发性肺纤维化的部分患者。从经典的DC到再生障碍性贫血这一广泛的疾病谱可被视为端粒维持缺陷性疾病——“端粒病”。这些进展增加了我们对正常造血的理解，并强调了端粒酶和端粒在人类生物学中的重要作用。它们还有助于DC的诊断（特别是在表现不典型时）和治疗。
Dyskeratosis congenita (DC) is a multisystem inherited syndrome exhibiting marked clinical and genetic heterogeneity. In its classic form, it is characterized by mucocutaneous abnormalities, BM failure, and a predisposition to cancer. BM failure is the principal cause of premature mortality. Studies over the last 15 years have led to significant advances, with 8 DC genes (DKC1, TERC, TERT, NOP10, NHP2, TIN2, C16orf57, and TCAB1) having been characterized. Seven of these are important in telomere maintenance either because they encode components of the telomerase enzyme complex (DKC1, TERC, TERT, NOP10, NHP2, and TCAB1) or the shelterin complex (TINF2). DC is therefore principally a disease of defective telomere maintenance and patients usually have very short telomeres. The genetic advances have led to the unification of DC with several other disorders, including the severe multisystem disorders Hoyeraal-Hreidarsson and Revesz syndromes, as well as a subset of patients with aplastic anemia, myelodysplasia, leukemia, and idiopathic pulmonary fibrosis. This wide spectrum of diseases ranging from classic DC to aplastic anemia can be regarded as disorders of defective telomere maintenance-"the telomereopathies." These advances have increased our understanding of normal hematopoiesis and highlighted the important role of telomerase and telomeres in human biology. They are also facilitating the diagnosis (especially when presentation is atypical) and management of DC.