EuroDBA

Diamond-Blackfan anemia (DBA) is a rare congenital bone marrow failure syndrome characterized by early onset red cell aplasia in addition to physical anomalies present in 50% of affected children. Therapeutic principles consist of transfusions, corticosteroids, or hematopoietic stem cell transplantation. However there are no predictors allowing for early treatment stratification. While mutations in ribosomal protein genes are found linked to DBA, underlying etiologies are unresolved in 1/3 of all patients. The EuroDBA consortium was established 2012 with the aim to identify novel genetic defects and to study the pathogenesis of DBA. We have since successfully adjoined the major European DBA patient registries, identified and characterized novel gene mutations, published studies revealing new molecular pathomechanisms, and achieved an exceptional level of global outreach to DBA investigators and patients. To continue this trajectory of success we first propose to expand the consortium to include the other European groups and assist them to establish national registries/biobanks and patient support groups. With this clinical platform we aim to harmonize clinical reporting and genetic testing and genotype/phenotype studies, to better define the non-hematological phenotype (“ribosomopathy” features) of DBA, and to identify disease biomarkers. For the categorization of known and novel genetic variants, we will perform functional analyses in a centralized fashion. These will include differentiation and ribosome biogenesis assays, rRNA/proteomic profiling, and zebrafish modeling.