Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan; Departments of Pediatrics and Cancer Biology, Cleveland Clinic, Cleveland, OH.
Departments of Pediatrics and Cancer Biology, Cleveland Clinic, Cleveland, OH.
Haematologica. 2023 Oct 1;108(10):2594-2605. doi: 10.3324/haematol.2023.282949.
Shwachman-Diamond syndrome is a rare inherited bone marrow failure syndrome characterized by neutropenia, exocrine pancreatic insufficiency, and skeletal abnormalities. In 10-30% of cases, transformation to a myeloid neoplasm occurs. Approximately 90% of patients have biallelic pathogenic variants in the SBDS gene located on human chromosome 7q11. Over the past several years, pathogenic variants in three other genes have been identified to cause similar phenotypes; these are DNAJC21, EFL1, and SRP54. Clinical manifestations involve multiple organ systems and those classically associated with the Shwachman-Diamond syndrome (bone, blood, and pancreas). Neurocognitive, dermatologic, and retinal changes may also be found. There are specific gene-phenotype differences. To date, SBDS, DNAJC21, and SRP54 variants have been associated with myeloid neoplasia. Common to SBDS, EFL1, DNAJC21, and SRP54 is their involvement in ribosome biogenesis or early protein synthesis. These four genes constitute a common biochemical pathway conserved from yeast to humans that involve early stages of protein synthesis and demonstrate the importance of this synthetic pathway in myelopoiesis.
Shwachman-Diamond 综合征是一种罕见的遗传性骨髓衰竭综合征，其特征为中性粒细胞减少症、外分泌胰腺功能不全和骨骼异常。在 10-30%的病例中，会转化为髓系肿瘤。大约 90%的患者在位于人类 7q11 染色体上的 SBDS 基因中存在双等位基因致病性变异。在过去的几年中，已经确定了另外三个基因中的致病性变异可导致类似的表型；这些是 DNAJC21、EFL1 和 SRP54。临床表现涉及多个器官系统，与经典的 Shwachman-Diamond 综合征（骨骼、血液和胰腺）相关。也可能发现神经认知、皮肤和视网膜的变化。存在特定的基因表型差异。迄今为止，SBDS、DNAJC21 和 SRP54 变体与髓系肿瘤相关。SBDS、EFL1、DNAJC21 和 SRP54 的共同点是它们参与核糖体生物发生或早期蛋白质合成。这四个基因构成了从酵母到人保守的共同生化途径，涉及蛋白质合成的早期阶段，并证明了该合成途径在髓系发生中的重要性。
