Molecular basis of Diamond-Blackfan anemia: new findings from the Italian registry and a review of the literature.

Diamond-Blackfan anemia (DBA) is a rare, pure red blood cell aplasia of childhood caused by an intrinsic defect in erythropoietic progenitors. Malformations occur in about 40% of patients. More than half of patients respond to steroids; non-responders need chronic transfusions or stem cell transplantation (SCT). Mutations in the gene encoding ribosomal protein S19 are found in 25% of patients, but the link with erythropoiesis is unclear. A second DBA locus has been found on chromosome 8p22-p23; analysis of genes of the region is in progress.,We present clinical and molecular data from 97 Italian DBA patients and a review of the literature.,We describe five new RPS19 gene mutations: four point mutations and one unbalanced chromosomal translocation. Hematologic findings, malformations and outcome are similar in the RPS19 mutated and the non-mutated groups. No genotype-phenotype correlation has been found so far in RPS19 mutated patients. Our data, however, and a thorough review of literature show a worse outcome (expressed as transfusion dependence) in patients with mutations that completely abolish one allele, i.e. gross chromosomal rearrangements and mutations at the initiation codon. The association of mental retardation with large deletions at the 19q locus points to a contiguous gene syndrome. A recurrent missense mutation (Arg62Trp) is associated with transfusion dependence in eight of the nine reported cases.,Nationwide collaboration and population-based registries recording molecular data are essential for the further dissection of this rare heterogeneous disease and the definition of new therapeutic trials.