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

Public Health Relevance

Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by severe anemia, birth defects, and cancer predisposition and is known to be caused by abnormalities of ribosomal protein genes in the majority of patients. The overarching goal of this project is to utilize the well-characterized patient population provided by the Diamond Blackfan Anemia Registry (DBAR) database to analyze treatment response and side effects, presence of birth defects in association with particular genes, and the development of cancer in order to improve care and access to clinical trials. Laboratory science utilizing the DBAR will ultimately provide new information regarding the molecular and cellular biology of ribosome abnormalities in acquired hematologic disorders such as myelodysplastic syndrome and some solid tumors.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL079571-14
Application #
9481847
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Qasba, Pankaj
Project Start
2004-09-30
Project End
2019-04-30
Budget Start
2018-05-01
Budget End
2019-04-30
Support Year
14
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Feinstein Institute for Medical Research
Department
Type
DUNS #
110565913
City
Manhasset
State
NY
Country
United States
Zip Code
11030
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