Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations
| Autor: | Emanuela Garelli, Paola Quarello, Carlo Dufour, Irma Dianzani, Fabrizio Loreni, Roberto Calabrese, Laura Biondini, Aldo Misuraca, Anna Aspesi, Alfredo Brusco, Adriana Carando, Ugo Ramenghi, Daniela Longoni, Luciana Vinti |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Ribosomal Proteins
Genotype Anemia Biology medicine.disease_cause Cell Line Cohort Studies hemic and lymphatic diseases Ribosomal protein S19 Diamond-Blackfan red cells bone marrow failure anemia medicine Humans Genetic Testing Diamond–Blackfan anemia Genetic Association Studies Anemia Diamond-Blackfan Mutation Settore BIO/11 Phenotype Italy Bone marrow failure Hematology Aplasia medicine.disease Transplantation Immunology Original Article |
| Zdroj: | Università degli Studi del Piemonte Orientale-IRIS |
| Popis: | 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; non-responders 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. |
| Databáze: | OpenAIRE |
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