Abstract
Diamond–Blackfan anemia (DBA) is an inherited red blood cell aplasia that usually presents during the first year of life. The main features of the disease are normochromic and macrocytic anemia, reticulocytopenia, and nearly absent erythroid progenitors in the bone marrow. The patients also present with growth retardation and craniofacial, upper limb, heart and urinary system congenital malformations in ~30–50 % of cases. The disease has been associated with point mutations and large deletions in ten ribosomal protein (RP) genes RPS19, RPS24, RPS17, RPL35A, RPL5, RPL11, RPS7, RPS10, RPS26, and RPL26 and GATA1 in about 60–65 % of patients. Here, we report a novel large deletion in RPL15, a gene not previously implicated to be causative in DBA. Like RPL26, RPL15 presents the distinctive feature of being required both for 60S subunit formation and for efficient cleavage of the internal transcribed spacer 1. In addition, we detected five deletions in RP genes in which mutations have been previously shown to cause DBA: one each in RPS19, RPS24, and RPS26, and two in RPS17. Pre-ribosomal RNA processing was affected in cells established from the patients bearing these deletions, suggesting a possible molecular basis for their pathological effect. These data identify RPL15 as a new gene involved in DBA and further support the presence of large deletions in RP genes in DBA patients.
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Acknowledgments
We wish to thank the patients and their families for participating in the study. This work was supported by the following Grants: NIH Grants R01 HL107558 and K02 HL111156, a Grant from the DBA Foundation (to H.T.G.), and a Grant from the Agence Nationale de la Recherche (RIBOCRASH) (to P.E.G.).
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Landowski, M., O’Donohue, MF., Buros, C. et al. Novel deletion of RPL15 identified by array-comparative genomic hybridization in Diamond–Blackfan anemia. Hum Genet 132, 1265–1274 (2013). https://doi.org/10.1007/s00439-013-1326-z
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DOI: https://doi.org/10.1007/s00439-013-1326-z