Whole genome profiling of fibroblasts from Diamond-Blackfan Anemia patients

Diamond-Blackfan Anemia (DBA) is a rare inherited red cell hypoplasia characterized by a defect in the maturation of erythroid progenitors and is in some cases associated to malformations. Patients have an increased risk of solid tumors. Mutations have been found in several ribosomal protein (RP) genes. Studies in hematopoietic progenitors from patients show that the haploinsufficiency of an RP impairs rRNA processing and ribosome biogenesis. DBA lymphocytes and fibroblasts show reduced protein synthesis, and the latter display abnormal rRNA processing and impaired proliferation. To evaluate the involvement of non-hematopoietic tissues in DBA, we have analyzed 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 statistically significantly differentially expressed in DBA patients' fibroblasts relative to controls. These genes include a large cluster of ribosomal proteins and factors involved in protein synthesis and amino acid metabolism, as well as genes with roles in cell death, cancer and tissue development. Our results report for the first time into abnormal expression in a non-hematopoietic cell type in DBA, and support the hypothesis that DBA may be due to a defect in general or specific protein synthesis. Keywords: Disease state analysis. Analyzed samples include fibroblasts from 4 DBA patients and 6 healthy controls.