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Diamond Blackfan Anemia at the Crossroad between Ribosome Biogenesis and Heme Metabolism

Diamond-Blackfan anemia (DBA) is a rare, pure red-cell aplasia that presents during infancy. Approximately 40% of cases are associated with other congenital defects, particularly malformations of the upper limb or craniofacial region. Mutations in the gene coding for the ribosomal protein RPS19 have...

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Autores principales: Chiabrando, Deborah, Tolosano, Emanuela
Formato: Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2864449/
https://www.ncbi.nlm.nih.gov/pubmed/20454576
http://dx.doi.org/10.1155/2010/790632
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author Chiabrando, Deborah
Tolosano, Emanuela
author_facet Chiabrando, Deborah
Tolosano, Emanuela
author_sort Chiabrando, Deborah
collection PubMed
description Diamond-Blackfan anemia (DBA) is a rare, pure red-cell aplasia that presents during infancy. Approximately 40% of cases are associated with other congenital defects, particularly malformations of the upper limb or craniofacial region. Mutations in the gene coding for the ribosomal protein RPS19 have been identified in 25% of patients with DBA, with resulting impairment of 18S rRNA processing and 40S ribosomal subunit formation. Moreover, mutations in other ribosomal protein coding genes account for about 25% of other DBA cases. Recently, the analysis of mice from which the gene coding for the heme exporter Feline Leukemia Virus subgroup C Receptor (FLVCR1) is deleted suggested that this gene may be involved in the pathogenesis of DBA. FLVCR1-null mice show a phenotype resembling that of DBA patients, including erythroid failure and malformations. Interestingly, some DBA patients have disease linkage to chromosome 1q31, where FLVCR1 is mapped. Moreover, it has been reported that cells from DBA patients express alternatively spliced isoforms of FLVCR1 which encode non-functional proteins. Herein, we review the known roles of RPS19 and FLVCR1 in ribosome function and heme metabolism respectively, and discuss how the deficiency of a ribosomal protein or of a heme exporter may result in the same phenotype.
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spelling pubmed-28644492010-05-07 Diamond Blackfan Anemia at the Crossroad between Ribosome Biogenesis and Heme Metabolism Chiabrando, Deborah Tolosano, Emanuela Adv Hematol Review Article Diamond-Blackfan anemia (DBA) is a rare, pure red-cell aplasia that presents during infancy. Approximately 40% of cases are associated with other congenital defects, particularly malformations of the upper limb or craniofacial region. Mutations in the gene coding for the ribosomal protein RPS19 have been identified in 25% of patients with DBA, with resulting impairment of 18S rRNA processing and 40S ribosomal subunit formation. Moreover, mutations in other ribosomal protein coding genes account for about 25% of other DBA cases. Recently, the analysis of mice from which the gene coding for the heme exporter Feline Leukemia Virus subgroup C Receptor (FLVCR1) is deleted suggested that this gene may be involved in the pathogenesis of DBA. FLVCR1-null mice show a phenotype resembling that of DBA patients, including erythroid failure and malformations. Interestingly, some DBA patients have disease linkage to chromosome 1q31, where FLVCR1 is mapped. Moreover, it has been reported that cells from DBA patients express alternatively spliced isoforms of FLVCR1 which encode non-functional proteins. Herein, we review the known roles of RPS19 and FLVCR1 in ribosome function and heme metabolism respectively, and discuss how the deficiency of a ribosomal protein or of a heme exporter may result in the same phenotype. Hindawi Publishing Corporation 2010 2010-05-05 /pmc/articles/PMC2864449/ /pubmed/20454576 http://dx.doi.org/10.1155/2010/790632 Text en Copyright © 2010 D. Chiabrando and E. Tolosano. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Chiabrando, Deborah
Tolosano, Emanuela
Diamond Blackfan Anemia at the Crossroad between Ribosome Biogenesis and Heme Metabolism
title Diamond Blackfan Anemia at the Crossroad between Ribosome Biogenesis and Heme Metabolism
title_full Diamond Blackfan Anemia at the Crossroad between Ribosome Biogenesis and Heme Metabolism
title_fullStr Diamond Blackfan Anemia at the Crossroad between Ribosome Biogenesis and Heme Metabolism
title_full_unstemmed Diamond Blackfan Anemia at the Crossroad between Ribosome Biogenesis and Heme Metabolism
title_short Diamond Blackfan Anemia at the Crossroad between Ribosome Biogenesis and Heme Metabolism
title_sort diamond blackfan anemia at the crossroad between ribosome biogenesis and heme metabolism
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2864449/
https://www.ncbi.nlm.nih.gov/pubmed/20454576
http://dx.doi.org/10.1155/2010/790632
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