Reduced gene expression of clustered ribosomal proteins in Diamond-Blackfan anemia patients without RPS19 gene mutations.

Diamond-Blackfan anemia (DBA) is a rare congenital pure red cell aplasia occasionally presenting physical anomalies. Ribosomal protein S19 gene (RPS19) is one of the causative genes for DBA; however, the pathologic mechanism of erythroblastopenia and abnormal morphology has not been clarified. To assess the pathophysiology of DBA, the gene expression profile of 2 representative patients carrying no RPS19 mutations was compared with that of aplastic anemia (AA) patients, assessed by the microarray analyses. The K-mean clustering analysis revealed the significant categorization of 28 ribosomal protein (RP) genes into a small set of group (994 genes) (P=2.39E-17), all of which were expressed at lower levels in DBA than in AA patients. RPS19 was categorized into the set of low expressing genes in DBA patients. No mutations were determined in the promoter and coding sequences of top 10 RP genes expressed at the levels over 1.2 of the AA/DBA ratio, in 3 DBA patients. These results indicated that the lower expression of RP gene group, even without the mutation, was a distinctive feature of DBA from AA, although the study number was small. The reduced RP gene expression, by itself, may suggest an underlying mechanism of the constitutional anemia.