Comparative analysis of Shwachman-Diamond syndrome to other inherited bone marrow failure syndromes and genotype-phenotype correlation
Comparative analysis of Shwachman-Diamond syndrome to other inherited bone marrow failure syndromes and genotype-phenotype correlation
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DOI：
10.1111/j.1399-0004.2010.01468.x
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发表时间：
2011-05-01
影响因子：
3.5
通讯作者：
Dror, Y.
中科院分区：
文献类型：
--
作者：
Hashmi, S. K.;Allen, C.;Dror, Y.
我们对遗传性骨髓衰竭综合征（IBMFS）表型的了解来自于仅研究一种IBMFS的病例报告或病例系列。然而，大量的表型重叠需要IBMFSs之间的比较分析。Shwachman-Diamond综合征（SDS）是一种IBMFS，对其临床表型的认识仍在不断发展。在这项分析中，我们使用了来自加拿大遗传性骨髓衰竭研究（CIMFS）的125例患者的数据，这是一项前瞻性多中心人群研究。对34例SDS患者进行了分析，并与CIMFS上最常见的4种IBMFS患者进行了比较：Diamond Blackfan贫血，Fanconi贫血（FA），Kostmann/重度先天性中性粒细胞减少症和先天性角化不良（DC）。SDS、FA和DC的诊断通常相对于症状发作延迟;这表明主要需要改进工具以建立快速诊断。我们确定了SDS和其他IBMFSs之间的多个表型差异，包括几个新的差异。SBDS双等位基因突变的频率低于以前的报告（81%）。重要的是，与双等位基因突变的患者相比，野生型SBDS患者的血液疾病更严重，但胰腺疾病较轻。总之，对IBMFSs的全面研究可以提供有用的疾病之间的比较数据。SBDS阴性SDS患者可能有更严重的血液学衰竭和轻度胰腺疾病。
Our knowledge of the phenotypes of inherited bone marrow failure syndromes (IBMFSs) derives from case reports or case series in which only one IBMFS was studied. However, the substantial phenotypic overlap necessitates comparative analysis between the IBMFSs. Shwachman-Diamond syndrome (SDS) is an IBMFS that the appreciation of what comprises its clinical phenotype is still evolving. In this analysis we used data on 125 patients from the Canadian Inherited Marrow Failure Study (CIMFS), which is a prospective multicenter population-based study. Thirty-four cases of SDS patients were analyzed and compared to other patients with the four most common IBMFSs on the CIMFS: Diamond Blackfan anemia, Fanconi anemia (FA), Kostmann/severe congenital neutropenia and dyskeratosis congenita (DC). The diagnosis of SDS, FA and DC was often delayed relative to symptoms onset; indicating a major need for improving tools to establish a rapid diagnosis. We identified multiple phenotypic differences between SDS and other IBMFSs, including several novel differences. SBDS biallelic mutations were less frequent than in previous reports (81%). Importantly, compared to patients with biallelic mutations, patients with wild type SBDS had more severe hematological disease but milder pancreatic disease. In conclusion, comprehensive study of the IBMFSs can provide useful comparative data between the disorders. SBDS-negative SDS patients may have more severe hematological failure and milder pancreatic disease.