Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA;
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Pediatric Hematology/Oncology, Seattle Children's Hospital, Seattle, WA; and Department of Pediatrics, University of Washington, Seattle, WA.
Blood. 2014 Oct 30;124(18):2784-92. doi: 10.1182/blood-2014-04-526301. Epub 2014 Sep 18.
Diamond-Blackfan anemia, Shwachman-Diamond syndrome, and dyskeratosis congenita are inherited syndromes characterized by marrow failure, congenital anomalies, and cancer predisposition. Genetic and molecular studies have uncovered distinct abnormalities in ribosome biogenesis underlying each of these 3 disorders. How defects in ribosomes, the essential organelles required for protein biosynthesis in all cells, cause tissue-specific abnormalities in human disease remains a question of fundamental scientific and medical importance. Here we review the overlapping and distinct clinical features of these 3 syndromes and discuss current knowledge regarding the ribosomal pathways disrupted in each of these disorders. We also explore the increasing complexity of ribosome biology and how this informs our understanding of developmental biology and human disease.
Diamond-Blackfan 贫血、Shwachman-Diamond 综合征和先天性角化不良是三种遗传性综合征，其特征为骨髓衰竭、先天畸形和癌症易感性。遗传和分子研究揭示了这三种疾病的核糖体生物发生的不同异常。核糖体是所有细胞中蛋白质生物合成所必需的细胞器，那么核糖体的缺陷如何导致人类疾病中的组织特异性异常仍然是一个具有基础科学和医学重要性的问题。在这里，我们回顾了这三种综合征的重叠和独特的临床特征，并讨论了目前关于这些疾病中每种疾病所破坏的核糖体途径的知识。我们还探讨了核糖体生物学日益增加的复杂性，以及这如何告知我们对发育生物学和人类疾病的理解。
