The European Ribosomopathy Consortium

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The ribosome is a fundamental piece of molecular machinery that is responsible for translating messages containing instructions for the synthesis of protein chains. A group of rare diseases, known as “ribosomopathies”, occur when inherited genetic mutations impair the synthesis or the function of ribosomes. Very often, these diseases result in a failure of the bone marrow to properly produce blood cells. The EuroDBA consortium was created in 2012 to bring together clinical and biological researchers working on the ribosomopathy Diamond-Blackfan anemia (DBA). Together we have registered at least 300 new DBA patients, discovered several new disease-linked genes, published ten collaborative peer-reviewed articles, and organized three international symposia. This new phase of the consortium, titled RiboEurope, will broaden the focus of the rare diseases we study to include other inherited bone marrow failures linked to deficient ribosome synthesis or function. We have been successful in biobanking cell lines from over 100 patients that have a known ribosomopathy such as DBA or Shwachman-Diamond syndrome (SDS), as well as about 1/3 of these who remain “unknown”. One major goal of this proposal is to perform in-depth profiling of all our biobanked cell lines. We will profile their metabolic signatures, the specific way ribosome biogenesis is impaired, and how these defects sensitize the cell to death signals. The goal here is to develop standardized diagnostic profiles that can be used to rapidly predict specific gene mutations. We will also bring a special focus to the groups of “unknown” patients in our registries where a ribosomopathy is suspected but no indicative gene mutation is evident. We have a pipeline in place for this “Solving the Unsolved”, which has already been successful in finding and characterizing several new genes that drive ribosomopathies and diseases that look like them.