The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia

Diamond-Blackfan anaemia (DBA) is a constitutional erythroblastopenia chara cterized by absent or decreased erythroid precursors. The disease, previous ly mapped to human chromosome 19q13, is frequently associated with a variet y of malformation. To identify the gene involved in DBA, we cloned the chro mosome 19q13 breakpoint in a patient with a reciprocal X; 19 chromosome tra nslocation. The breakpoint occurred in the gene encoding ribosomal protein S19. Furthermore, we identified mutations in RPS19 in 10 of 40 unrelated DM A patients, including nonsense, frameshift, splice site and missense mutati ons, as well as two intragenic deletions. These mutations are associated wi th clinical features that suggest a function for RPS19 in erythropoiesis an d embryogenesis.