BMC Genomics Research article Fibroblasts from patients with Diamond-Blackfan anaemia show abnormal expression of genes involved in protein synthesis, amino acid metabolism and cancer Federica Avondo1, Paola Roncaglia2, Nicoletta Crescenzio3, Helena Krmac2, Emanuela Garelli3, Marta Armiraglio1, Carlotta Castagnoli4, Maria Francesca Campagnoli3, Ugo Ramenghi3, Stefano Gustincich2, Claudio Santoro1 and Irma Dianzani*1 BioMed Central Open Access Address: 1Department of Medical Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy, 2International School for Advanced Studies (SISSA/ISAS), Trieste, Italy, 3Department of Pediatric Sciences, Università di Torino, Torino, Italy and 4Azienda Ospedaliera CTO/CRF/Maria Adelaide, Torino, Italy Email: Federica Avondo - avondo@med.unipmn.it; Paola Roncaglia - roncagli@sissa.it; Nicoletta Crescenzio - nicoletta.crescenzio@unito.it; Helena Krmac - krmac@sissa.it; Emanuela Garelli - emanuela.garelli@unito.it; Marta Armiraglio - armiral@med.unipmn.it; Carlotta Castagnoli - ccastagnoli@hotmail.com; Maria Francesca Campagnoli - mariafrancesca.campagnoli@unito.it; Ugo Ramenghi - ugo.ramenghi@unito.it; Stefano Gustincich - gustinci@sissa.it; Claudio Santoro - csantoro@med.unipmn.it; Irma Dianzani* - irma.dianzani@med.unipmn.it * Corresponding author Published: 18 September 2009 BMC Genomics 2009, 10:442 doi:10.1186/1471-2164-10-442 This article is available from: http://www.biomedcentral.com/1471-2164/10/442 Received: 19 January 2009 Accepted: 18 September 2009 © 2009 Avondo et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Diamond-Blackfan anaemia (DBA) is a rare inherited red cell hypoplasia characterised by a defect in the maturation of erythroid progenitors and in some cases associated with malformations. Patients have an increased risk of solid tumors. Mutations have been found in several ribosomal protein (RP) genes, i.e RPS19, RPS24, RPS17, RPL5, RPL11, RPL35A. Studies in haematopoietic progenitors from patients show that haplo-insufficiency of an RP impairs rRNA processing and ribosome biogenesis. DBA lymphocytes show reduced protein synthesis and fibroblasts display abnormal rRNA processing and impaired proliferation. Results: To evaluate the involvement of non-haematopoietic tissues in DBA, we have analysed global gene expression in fibroblasts from DBA patients compared to healthy controls. Microarray expression profiling using Affymetrix GeneChip Human Genome U133A 2.0 Arrays revealed that 421 genes are differentially expressed in DBA patient fibroblasts. These genes include a large cluster of ribosomal proteins and factors involved in protein synthesis and amino acid metabolism, as well as genes associated to cell death, cancer and tissue development. Conclusion: This analysis reports for the first time an abnormal gene expression profile in a non- haematopoietic cell type in DBA. These data support the hypothesis that DBA may be due to a defect in general or specific protein synthesis. Page 1 of 12 (page number not for citation purposes)