Blood Journal
Leading the way in experimental and clinical research in hematology

Ribosomal protein gene deletions in Diamond-Blackfan anemia

  1. Jason E. Farrar1,
  2. Adrianna Vlachos2,3,
  3. Eva Atsidaftos2,
  4. Hannah Carlson-Donohoe4,
  5. Thomas C. Markello4,
  6. Robert J. Arceci1,
  7. Steven R. Ellis5,
  8. Jeffrey M. Lipton2,3, and
  9. David M. Bodine6
  1. 1Division of Pediatric Oncology, Department of Oncology, Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD;
  2. 2Feinstein Institute for Medical Research, Patient-Oriented Research, Manhasset, NY;
  3. 3Division of Hematology/Oncology and Stem Cell Transplantation, Steven and Alexandra Cohen Children's Medical Center of New York, New Hyde Park, NY;
  4. 4Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD;
  5. 5Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY; and
  6. 6Hematopoiesis Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD


Diamond-Blackfan anemia (DBA) is a congenital BM failure syndrome characterized by hypoproliferative anemia, associated physical abnormalities, and a predisposition to cancer. Perturbations of the ribosome appear to be critically important in DBA; alterations in 9 different ribosomal protein genes have been identified in multiple unrelated families, along with rarer abnormalities of additional ribosomal proteins. However, at present, only 50% to 60% of patients have an identifiable genetic lesion by ribosomal protein gene sequencing. Using genome-wide single-nucleotide polymorphism array to evaluate for regions of recurrent copy variation, we identified deletions at known DBA-related ribosomal protein gene loci in 17% (9 of 51) of patients without an identifiable mutation, including RPS19, RPS17, RPS26, and RPL35A. No recurrent regions of copy variation at novel loci were identified. Because RPS17 is a duplicated gene with 4 copies in a diploid genome, we demonstrate haploinsufficient RPS17 expression and a small subunit ribosomal RNA processing abnormality in patients harboring RPS17 deletions. Finally, we report the novel identification of variable mosaic loss involving known DBA gene regions in 3 patients from 2 kindreds. These data suggest that ribosomal protein gene deletion is more common than previously suspected and should be considered a component of the initial genetic evaluation in cases of suspected DBA.

  • Submitted August 25, 2011.
  • Accepted October 26, 2011.
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