Ribosome synthesis disorders in Diamond-Blackfan anemia


DBA is a rare congenital erythroblastopenia (5-7 cases per million/live births) linked to mutations in ribosomal protein genes. Since the discovery in 1999 of heterozygous mutations in the ribosomal protein gene RPS19 in 25% of DBA patients, DBA has become a paradigm for ribosomal diseases. Our group was first to suggest that defects in ribosome biogenesis laid at the heart of the pathophysiological mechanism in DBA. Since then, we have been characterizing the functional impact of DBA mutations in various ribosomal protein genes involved in DBA identified through high-throughput and whole exome sequencing methods. To date, more than ribosomal protein genes were found to be haploinsufficient in subclasses of DBA patients, covering roughly 60-70% of the patients. Genes mutated in DBA patients still remain to be characterized. The precise pathological mechanisms generated by these mutations are ill understood, as well as the reason why they primarily affect erythropoiesis. This work is led in collaboration with Dr. Hanna Gazda (Boston Children's Hospital), Drs. Lydie Da Costa and Thierry Leblanc (Hôpital Robert Debré, Paris) and the EuroDBA e-Rare consortium (http://www.eurodba.eu/).



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