Human Genetics

, Volume 132, Issue 11, pp 1265–1274

Novel deletion of RPL15 identified by array-comparative genomic hybridization in Diamond–Blackfan anemia

  • Michael Landowski
  • Marie-Françoise O’Donohue
  • Christopher Buros
  • Roxanne Ghazvinian
  • Nathalie Montel-Lehry
  • Adrianna Vlachos
  • Colin A. Sieff
  • Peter E. Newburger
  • Edyta Niewiadomska
  • Michal Matysiak
  • Bertil Glader
  • Eva Atsidaftos
  • Jeffrey M. Lipton
  • Alan H. Beggs
  • Pierre-Emmanuel Gleizes
  • Hanna T. Gazda
Original Investigation

DOI: 10.1007/s00439-013-1326-z

Cite this article as:
Landowski, M., O’Donohue, MF., Buros, C. et al. Hum Genet (2013) 132: 1265. doi:10.1007/s00439-013-1326-z

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.

Supplementary material

439_2013_1326_MOESM1_ESM.pdf (207 kb)
Supplementary material 1 (PDF 207 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Michael Landowski
    • 1
  • Marie-Françoise O’Donohue
    • 2
    • 3
  • Christopher Buros
    • 1
  • Roxanne Ghazvinian
    • 1
  • Nathalie Montel-Lehry
    • 2
    • 3
  • Adrianna Vlachos
    • 4
    • 5
  • Colin A. Sieff
    • 6
    • 7
  • Peter E. Newburger
    • 8
  • Edyta Niewiadomska
    • 9
  • Michal Matysiak
    • 9
  • Bertil Glader
    • 10
  • Eva Atsidaftos
    • 4
    • 5
  • Jeffrey M. Lipton
    • 4
    • 5
  • Alan H. Beggs
    • 1
    • 7
  • Pierre-Emmanuel Gleizes
    • 2
    • 3
  • Hanna T. Gazda
    • 1
    • 7
  1. 1.Division of Genetics and Program in Genomics, The Manton Center for Orphan Disease ResearchBoston Children’s HospitalBostonUSA
  2. 2.Laboratoire de Biologie Moleculaire EucaryoteUniversite de ToulouseToulouseFrance
  3. 3.CNRS, UMR 5099ToulouseFrance
  4. 4.Feinstein Institute for Medical ResearchManhassetUSA
  5. 5.Division of Hematology/Oncology and Stem Cell TransplantationSteven and Alexandra Cohen Children’s Medical CenterNew Hyde ParkUSA
  6. 6.Division of Pediatric HematologyBoston Children’s HospitalBostonUSA
  7. 7.Harvard Medical SchoolBostonUSA
  8. 8.Department of PediatricsUniversity of Massachusetts Medical SchoolWorcesterUSA
  9. 9.Department of Paediatric Haematology/OncologyMedical University of WarsawWarsawPoland
  10. 10.Division of Pediatric Hematology/OncologyStanford University School of MedicineStanfordUSA

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