MUTATIONS IN THE ERYTHROPOIETIN RECEPTOR GENE ARE NOT A COMMON-CAUSE OF DIAMOND-BLACKFAN ANEMIA

Diamond-Blackfan anemia (DBA) is an inherited pure red blood cell apla sia that often requires lifelong transfusional support. The origin of the imperfect erythrogenesis is not known. The existence of more than one molecular basis for DBA is indicated by its different modes of inh eritance and widely variable clinical phenotypes, Several erythroid gr owth factors have been thought to have a role in the pathogenesis of D BA. However, there is neither molecular nor clinical evidence for the involvement of stem cell factor or interleukin-3. The observation of e levated erythropoietin (EPO) concentrations and an impaired in vivo an d in vitro response to pharmacologic doses of recombinant human EPO ha s suggested a defective EPO function in the pathogenesis of DBA. We ha ve investigated the possible involvement of the EPO receptor (EPO-R) g ene in 23 patients by screening its coding sequence for mutations usin g single-strand conformation polymorphism (SSCP). A Southern blot and hybridization with an EPO-R probe was also performed on DNA from seven patients. No causal mutations were identified. The absence of concord ant segregation of the disease with the EPO-R gene in two informative families ruled out its role in their DBA children. These findings demo nstrate that DBA is not commonly associated with EPO-R gene mutations. (C) 1996 by The American Society of Hematology.