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

 描述（由申请人提供）：Diamond Blackfan贫血登记处（DBAR）是一个罕见的遗传性骨髓衰竭综合征（DBA）患者的综合数据库。DBA是一种异质性遗传疾病，其特征是纯红细胞再生障碍性贫血、先天性异常和癌症易感性。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。到46岁，癌症的总体累积发病率超过20%，与一般人群相比，一些个体癌症风险（如结肠癌和骨肉瘤）升高超过30倍。迄今为止，已发现11个编码核糖体蛋白质的小亚基和大亚基的基因发生突变，占DBA患者的近70%。同一家庭中的受影响个体在贫血程度、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差异很大。在开发DBAR之前，我们关于流行病学和对各种治疗方式的反应的知识完全来自文献报告。开发DBAR是为了提供与生物样品相关的良好表征的患者底物，从而允许DBA的流行病学和生物学研究。本提案的目的是继续改进和利用DBAR，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，以促进发现新基因时的基因型-表型相关性3）提供良好表征的患者获得治疗方案4）为患者及其医疗保健提供者提供研究5）为患者及其医疗保健提供者提供研究结果6）作为患者及其医生的资源，以指导诊断，治疗，7）为DBA开发准确、快速的诊断测试8）利用DBAR基础设施和患者数据开发和管理临床试验9）寻求国家和国际合作研究

 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 overall cumulative incidence of cancer is over 20% by age 46, with some individual cancer risks such as colon carcinoma and osteogenic sarcoma elevated more than 30-fold compared to the general population. To date, 11 genes encoding ribosomal proteins of both the small and large subunits have been found to be mutated, representing nearly 70% of patients with DBA. Affected individuals within the same family 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 was 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 proposal is to continue 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 as new genes are discovered 3) provide well-characterized patients access 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, rapid diagnostic test for DBA 8) utilize the DBAR infrastructure and patient data to develop and manage clinical trials 9) solicit national and international collaborative research