Abstract
Diamond–Blackfan anaemia (DBA) is a constitutional erythroblastopenia characterized by absent or decreased erythroid precursors. The disease, previously mapped to human chromosome 19q13, is frequently associated with a variety of malformations. To identify the gene involved in DBA, we cloned the chromosome 19q13 breakpoint in a patient with a reciprocal X;19 chromosome translocation. The breakpoint occurred in the gene encoding ribosomal protein S19. Furthermore, we identified mutations in RPS19 in 10 of 40 unrelated DBA patients, including nonsense, frameshift, splice site and missense mutations, as well as two intragenic deletions. These mutations are associated with clinical features that suggest a function for RPS19 in erythropoiesis and embryogenesis.
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Acknowledgements
We are grateful to the patients and their families for their participation in this study. We thank O. Nygård and H. Johansson for discussions; L. Gordon for cosmids in the 19q13 region; and the European DBA consortium of the European Society for Pediatric Hematology and Immunology and the Resource Center of the German Human Genome Project, Berlin. This work was supported by grants from the Children's Cancer Foundation of Sweden, the Swedish Medical Research Council, the DBA Foundation Inc., T. and R. Söderbergs Fund, The Swedish Cancer Society, The Beijer Foundation, the Borgström Foundation, Ronald McDonalds fund, Lundbergs Foundation, Wera Ekström's fund, Uppsala University, Association Française Contre les Myopathies, Généthon and DRC (CRC 950183) AP–HP, Telethon Italia (grant E.619), NIH grants DK 32094 and DK 26263 and Max Reinhart Charitable Trust.
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Draptchinskaia, N., Gustavsson, P., Andersson, B. et al. The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia. Nat Genet 21, 169–175 (1999). https://doi.org/10.1038/5951
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DOI: https://doi.org/10.1038/5951
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