title: Fibroblasts from patients with Diamond-Blackfan anaemia show abnormal expression of genes involved in protein synthesis, amino acid metabolism and cancer.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy. avondo@med.unipmn.it
authors.forename: Federica
authors.initials: F
authors.lastname: Avondo
authors.forename: Paola
authors.initials: P
authors.lastname: Roncaglia
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Crescenzio
authors.forename: Helena
authors.initials: H
authors.lastname: Krmac
authors.forename: Emanuela
authors.initials: E
authors.lastname: Garelli
authors.forename: Marta
authors.initials: M
authors.lastname: Armiraglio
authors.forename: Carlotta
authors.initials: C
authors.lastname: Castagnoli
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Campagnoli
authors.forename: Ugo
authors.initials: U
authors.lastname: Ramenghi
authors.forename: Stefano
authors.initials: S
authors.lastname: Gustincich
authors.forename: Claudio
authors.initials: C
authors.lastname: Santoro
authors.forename: Irma
authors.initials: I
authors.lastname: Dianzani
mesh_terms: D029503:Anemia, Diamond-Blackfan / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D014176:Protein Biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000235:genetics*
chemical_list: D012269:Ribosomal Proteins; C040343:ribosomal protein S19