Clinical spectrum and molecular pathophysiology of Shwachman-Diamond syndrome.
Clinical spectrum and molecular pathophysiology of Shwachman-Diamond syndrome.
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Shwachman-Diamond 综合征的临床谱和分子病理生理学。
DOI：
10.1097/moh.0b013e32834114a5
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发表时间：
2011-01
影响因子：
3.2
通讯作者：
Shimamura A
中科院分区：
文献类型：
--
作者：
Huang JN;Shimamura A
Shwachman Diamond 综合征 (SDS) 是一种遗传性骨髓衰竭和癌症易感综合征，影响多个器官系统。大多数患者中都发现了 SBDS 基因突变，但 SBDS 蛋白产物的分子功能仍不清楚。在这里，我们回顾了 SDS 临床和分子表征的最新进展。新数据支持 SBDS 蛋白的多功能作用。目前的研究表明，SBDS 在 60S 大核糖体亚基成熟和有丝分裂纺锤体稳定中发挥作用。最近的数据表明，它还可能影响肌动蛋白聚合、液泡 pH 调节和 DNA 代谢。 SBDS 缺失会导致造血细胞固有缺陷以及骨髓基质异常。 SDS 是一种多系统疾病，由参与多个重要细胞过程的蛋白质缺陷引起。阐明 SBDS 的分子功能将为了解核糖体生物发生和有丝分裂纺锤体稳定性缺陷如何导致造血衰竭、癌症易感性和异常提供重要见解。
Shwachman Diamond syndrome (SDS) is an inherited bone marrow failure and cancer predisposition syndrome that affects multiple organ systems. Mutations in the SBDS gene are found in the majority of patients, but the molecular function of the SBDS protein product remains unclear. Here, we review recent progress in the clinical and molecular characterization of SDS. Emerging data support a multifunctional role for the SBDS protein. Current studies indicate that SBDS functions in 60S large ribosomal subunit maturation and in mitotic spindle stabilization. Recent data suggest it may also affect actin polymerization, vacuolar pH regulation and DNA metabolism. SBDS loss results in both hematopoietic cell-intrinsic defects as well as marrow stromal abnormalities. SDS is a multisystemic disease arising from defects in a protein that participates in several essential cellular processes. Elucidating the molecular function of SBDS will provide important insights into how defects in ribosome biogenesis and mitotic spindle stabilization result in hematopoietic failure, cancer predisposition, and abnormalities.