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Diamond-Blackfan anemia, a disease of the ribosome |
Hématologie. Volume 15, Number 1, 20-34, janvier-février 2009, Revue
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 Résumé
Texte intégral
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Author(s) : Lydie Da Costa, Alexis Proust, Hélène Moniz, Corinne Hurtaud, Isabelle Marie, Gil Tchernia, Thierry Leblanc |
Summary : Diamond-Blackfan anemia (DBA) is a rare congenital erythroblastopenia with, in 40% of DBA cases, growth retardation and various malformations, mostly in the cephalic area and in the extremities. In 1997, a 7 year-old DBA girl, from Sweden, carried a balanced translocation 46, XX, t(X\;19). She was at the origin of DBA genetic story and led to the discovery of the first gene involved in DBA, the ribosomal protein S19 gene (RPS19). DBA was the first disease related to a ribosomal defect. Knock-out mouse animal models was unable to decipher the mechanistic understanding of DBA pathophysiology. By contrast, depletion of one of the two rps19 genes (rps19A or rps19B) in yeast, S. cerevisiae, identified the defect of ribosomal biogenesis. DBA is related to a defect in ribosomal RNA (RNAr) maturation and in particular, in the pre-particule 40S maturation. Strikingly, the defect in ribosome assembly has been found in EBV infected lymphoblastoid cells and in skin fibroblasts from DBA patients. This pointed out the fact that DBA is a ribosomal disease. After DBA, other diseases, cartilage hair hypoplasia, congenita dyskeratosis, Shawchman-Diamond syndrome, Treacher Collins syndrome, have also been related to a ribosomal defect (RNAr defect in the first three, DNAr defect in the Treacher Collins syndrome). Recently, it is an acquired hematological disease, the minus 5q syndrome, a myelodysplastic syndrome, which has been found linked to a ribosomal protein defect. Minus 5q syndrome is due to RPS14 gene haploinsufficiency. Ribosomal diseases are usually characterized by bone marrow failure in one or more lineages, a risk of malignancies and are related to genes coding for proteins, which are localized into the cell nucleoli, reinforcing their role in ribosome biogenesis. Since RPS19 gene, other genes involved in DBA have been identified. All of them are ribosomal protein genes: RPS17, RPS24, RPL5, RPL11, and RPL35a genes and others genes on their way. For the first time, some genes from the large ribosomal subunit are involved. This reinforces definitely DBA as a disease of the ribosome. However, we have currently no clue regarding the erythroid tropism of the disease. |
Keywords : Diamond-Blackfan anemia, erythroblastopenia, RPS19, RPS24, RPL5, RPL11, ribosome |
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