A Vital Tool for the Study of DBA:The Diamond Blackfan Anemia Registry

描述（由申请人提供）：Diamond Blackfan Anemia Registry （DBAR）是一个罕见的遗传性骨髓衰竭综合征Diamond Blackfan Anemia （DBA）患者的综合数据库。DBA是一种异质性遗传疾病，其特征是纯红细胞发育不全、先天性异常和易患癌症。贫血通常出现在婴儿期或幼儿期，大约50%的患者至少有一种先天性异常。精算癌症风险虽然增加了，但目前还不确定。到目前为止，已经发现有6个编码核糖体蛋白的基因发生了突变，包括小亚基和大亚基，占DBA患者的近50%。值得注意的是，同一家庭中“受影响”的个体在贫血程度、对皮质类固醇的反应、先天性异常的存在和癌症的发展方面可能存在巨大差异。在开发DBAR之前，我们对流行病学和对各种治疗方式的反应的了解完全来自文献报道。开发DBAR是为了提供与生物样本相关联的具有良好特征的患者底物，从而允许对DBA的流行病学和生物学进行研究。本应用程序的目的是改进和开发DBA，以便：1)促进对DBA的流行病学和生物学的调查；2)提供DBA患者的准确表型，促进基因型-表型的相关性；3)为特征良好的患者提供治疗方案；4)为患者及其卫生保健提供者提供获得研究的机会；5)向患者及其卫生保健提供者提供研究结果；6)为患者及其医生提供资源，指导诊断、治疗和生育决策；7)开发准确、快速的DBA诊断筛选试验；8)鼓励国内和国际合作研究。

DESCRIPTION (provided by applicant): The Diamond Blackfan Anemia Registry (DBAR) is a comprehensive database of patients with the rare inherited bone marrow failure syndrome Diamond Blackfan anemia (DBA). DBA is a heterogeneous genetic disorder characterized by pure red cell aplasia, congenital anomalies and a predisposition to cancer. Anemia usually presents in infancy or early childhood and approximately 50% of patients have at least one congenital anomaly. The actuarial cancer risk although increased, is as of yet, undetermined. To date six genes encoding ribosomal proteins, of both the small and large subunits, have been found to be mutated, representing nearly 50% of patients with DBA. Of note, "affected" individuals within the same family may vary dramatically as to the degree of anemia, response to corticosteroids, the presence of congenital anomalies and the development of cancer. Prior to the development of the DBAR our knowledge regarding the epidemiology and response to various treatment modalities was determined exclusively from literature reports. The DBAR has been developed in order to provide a well-characterized patient substrate linked to biological samples, permitting the study of the epidemiology and biology of DBA. The objective of this application is to improve and exploit the DBAR in order to: 1) facilitate investigations into the epidemiology and biology of DBA; 2) provide an accurate phenotype of DBA patients to facilitate genotype-phenotype correlations; 3) provide access of well characterized patients to treatment protocols; 4) provide patients and their health care providers access to research studies; 5) provide patients and their health care providers with results of research studies; 6) serve as a resource to patients and their doctors to guide diagnostic, therapeutic, and reproductive decisions; 7) develop an accurate and rapid diagnostic screening test for DBA; and 8) encourage national and international collaborative research. PUBLIC HEALTH RELEVANCE: By exploiting a well-characterized patient population, the Diamond Blackfan Anemia Registry, the molecular basis of red blood cell production and its link to ribosome assembly and function and cancer predisposition, can be explored. The goal of this project is to utilize this database for detailed analysis of the degree of anemia, treatment response, and presence of congenital anomalies and development of cancer in DBA patients. This will lead to insights into the etiology of birth defects and cancer in these patients and in the population at large and ultimately lead to improved clinical care for DBA patients.