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Cited by 233Blood disorders and treatmentsGenomics and Rare DiseasesRNA and protein synthesis mechanisms

The ribosomal basis of diamond-blackfan anemia: mutation and database update

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Boria, Ilenia, Garelli, Emanuela, Gazda, Hanna T., Aspesi, Anna, Quarello, Paola, Pavesi, Elisa, Ferrante, Daniela, Meerpohl, Joerg J. +21 more·2010·Human Mutation
DOI 10.1002/humu.21383PMC PMC4485435
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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.

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Authors
Boria, I., Garelli, E., Gazda, H. T., Aspesi, A., Quarello, P., Pavesi, E., Ferrante, D., Meerpohl, J. J., Kartal, M., Da Costa, L., Proust, A., Leblanc, T., Simansour, M., Dahl, N., Fröjmark, A.-S., Pospisilova, D., Cmejla, R., Beggs, A. H., Sheen, M. R., Landowski, M., M. Buros, C., M. Clinton, C., J. Dobson, L., Vlachos, A., Atsidaftos, E., Lipton, J. M., Ellis, S. R., Ramenghi, U., & Dianzani, I.
Affiliations
  • Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT)
  • University of Turin (IT)
  • Boston Children's Hospital (US)
  • University of Freiburg (DE)
  • Bicêtre Hospital (FR)
  • Assistance Publique – Hôpitaux de Paris (FR)
  • Uppsala University (SE)
  • Feinstein Institute for Medical Research (US)
  • University of Louisville (US)
Corresponding author
Dianzani, Irma
ORCID
Venue
Human Mutation
Publisher
Wiley
Published
2010-11-22
Volume
31
Issue
12
Pages
1269-1279
ISSN
1059-7794 (ISSN-L)
DOI
10.1002/humu.21383
PMC
PMC4485435
OpenAlex
W2027349434
Cited by
233
References
1
Citations by year
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FWCI
8.30
Type
journal article
Language
en
Open access
Licence
doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 1744 d)
Locations
  • Human Mutation (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • HAL (submittedVersion, other-oa)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
  • Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R01HL079571)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR044345)
  • National Center for Research Resources (M01RR018535)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
Diamond-Blackfan anemia, ribosomal proteins, ribosome biogenesis, de novo mutations, inherited mutations, CpG, gene conversion, genotype-phenotype correlation, RPL5, ribosomal protein L11, malformations
MeSH terms
Base Sequence, Humans, Molecular Sequence Data, Mutation, Ribosomal Proteins, Ribosomes, Mutagenesis, Anemia, Diamond-Blackfan, Databases, Genetic, Genetic Association Studies

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