The European Ribosomopathy Consortium

核糖体是一种基本的分子机器，负责翻译含有合成蛋白质链指令的信息。当遗传基因突变损害核糖体的合成或功能时，就会发生一组罕见的疾病，称为核糖病。通常，这些疾病会导致骨髓不能正常产生血细胞。EuroDBA联盟成立于2012年，目的是将研究核糖体病钻石-布莱克凡贫血(DBA)的临床和生物研究人员聚集在一起。我们总共登记了至少300名新的DBA患者，发现了几个新的与疾病相关的基因，发表了10篇合作同行评议文章，并组织了三次国际研讨会。该联盟的这个名为RiboEurope的新阶段将扩大我们研究的罕见疾病的重点，将其他与核糖体合成或功能缺陷有关的遗传性骨髓衰竭包括在内。我们已经成功地对100多名患有已知核糖体疾病(如DBA或Shwachman-Diamond综合征(SDS))的患者的细胞系进行了生物库筛选，其中约三分之一的患者仍处于“未知”状态。这项提案的一个主要目标是对我们所有的生物库细胞系进行深入的分析。我们将描述它们的代谢特征，核糖体生物发生受损的具体方式，以及这些缺陷如何使细胞对死亡信号敏感。这里的目标是开发标准化的诊断图谱，可以用来快速预测特定的基因突变。我们还将特别关注我们登记的“未知”患者群体，这些患者被怀疑患有核糖体病，但没有明显的指示性基因突变。我们已经有了一条解决未解之谜的管道，已经成功地发现并鉴定了几个驱动核糖体疾病和类似疾病的新基因。

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.