The ribosomal basis of diamond-blackfan anemia: mutation and database update
Open Access
- 19 October 2010
- journal article
- mutation update
- Published by Hindawi Limited in Human Mutation
- Vol. 31 (12), 1269-1279
- https://doi.org/10.1002/humu.21383
Abstract
Diamond‐Blackfan Anemia (DBA) is characterized by a defect of erythroid progenitors and, clinically, by anemia and malformations. DBA exhibits an autosomal dominant pattern of inheritance with incomplete penetrance. Currently nine genes, all encoding ribosomal proteins (RP), have been found mutated in approximately 50% of patients. Experimental evidence supports the hypothesis that DBA is primarily the result of defective ribosome synthesis. By means of a large collaboration among six centers, we report here a mutation update that includes nine genes and 220 distinct mutations, 56 of which are new. The DBA Mutation Database now includes data from 355 patients. Of those where inheritance has been examined, 125 patients carry a de novo mutation and 72 an inherited mutation. Mutagenesis may be ascribed to slippage in 65.5% of indels, whereas CpG dinucleotides are involved in 23% of transitions. Using bioinformatic tools we show that gene conversion mechanism is not common in RP genes mutagenesis, notwithstanding the abundance of RP pseudogenes. Genotype–phenotype analysis reveals that malformations are more frequently associated with mutations in RPL5 and RPL11 than in the other genes. All currently reported DBA mutations together with their functional and clinical data are included in the DBA Mutation Database. Hum Mutat 31:1269–1279, 2010.Keywords
This publication has 51 references indexed in Scilit:
- Severe iron overload in Blackfan‐Diamond anemia: A case‐control studyAmerican Journal of Hematology, 2009
- Identification of mutations in the ribosomal protein L5 (RPL5) and ribosomal protein L11 (RPL11) genes in Czech patients with Diamond-Blackfan anemiaHuman Mutation, 2009
- Loss of Ribosomal Protein L11 Affects Zebrafish Embryonic Development through a p53-Dependent Apoptotic ResponsePLOS ONE, 2009
- Gene therapy of Diamond Blackfan anemia CD34+ cells leads to improved erythroid development and engraftment following transplantationExperimental Hematology, 2008
- Assembly factors Rpf2 and Rrs1 recruit 5S rRNA and ribosomal proteins rpL5 and rpL11 into nascent ribosomesGenes & Development, 2007
- Ribosomal protein S17 gene (RPS17) is mutated in Diamond-Blackfan anemiaHuman Mutation, 2007
- Ribosomal Protein S24 Gene Is Mutated in Diamond-Blackfan AnemiaAmerican Journal of Human Genetics, 2006
- Molecular basis of Diamond-Blackfan anemia: new findings from the Italian registry and a review of the literature.2004
- Mutations in ribosomal protein S19 gene and diamond blackfan anemia: wide variations in phenotypic expression.1999
- Elevated red cell adenosine deaminase activity: a marker of disordered erythropoiesis in Diamond‐Blackfan anaemia and other haematologic diseasesBritish Journal of Haematology, 1988