Diamond-blackfan anemia: Genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations

Paola Quarello, Emanuela Garelli, Adriana Carando, Alfredo Brusco, Roberto Calabrese, Carlo Dufour, Daniela Longoni, Aldo Misuraca, Luciana Vinti, Anna Aspesi, Laura Biondini, Fabrizio Loreni, Irma Dianzani, Ugo Ramenghi

Research output: Contribution to journalArticlepeer-review


Background: Diamond-Blackfan anemia is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. Anemia is corrected by steroid treatment in more than 50% of cases; nonresponders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of Diamond-Blackfan anemia and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that Diamond-Blackfan anemia is a disorder of ribosome biogenesis. Two new genes (RPL5, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. Design and Methods: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, RPL5, RPL11, and RPL35A in 92 Italian patients with Diamond-Blackfan anemia who were negative for RPS19 mutations. Results: About 20% of the patients screened had mutations in RPL5 or RPL11, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic malformations in patients with RPL5 and RPL11 mutations. A close association was evident between RPL5 mutations and craniofacial malformations, and between hand malformations and RPL11 mutations. Conclusions: Mutations in four ribosomal proteins account for around 50% of all cases of Diamond-Blackfan anemia in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and RPL11 in patients with Diamond-Blackfan anemia with malformations.

Original languageEnglish
Pages (from-to)206-213
Number of pages8
Issue number2
Publication statusPublished - Feb 2010


  • Anemia
  • Bone marrow failure
  • DBA
  • Red cells
  • Ribosomal proteins

ASJC Scopus subject areas

  • Hematology


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