A novel intrachromosomal rearrangement in the beta-globin gene found in an African-American family

We describe here a deletion of 34 nucleotides from the 3' end of the first intervening sequence of the beta-globin gene covering the AGGC splice junction, and the insertion of 32 nucleotides of the delta-globin gene at the same location. This gene rearrangement was detected in three members of an African-American family. The proband, a 28-year-old female, and her mother had a history of chronic anemia. One of her two brothers, who inherited the same gene defect, was apparently healthy with no symptoms of hemolytic anemia. The proband, her rather, and her two brothers, including the one who carried the beta-globin gene rearrangement, were found to be heterozygous for alpha-thalassemia-2 (-alpha(3.7)). Although the AGGC splice junction is disrupted (AGGC-->AGAT), the invariant AG has remained intact after this gene rearrangement. Our investigations could not detect any defect in RNA processing in the affected beta-globin genes. The discrepancies between the phenotypes and the globin chain synthesis ratios of the mother, her daughter, and her son who inherited the same gene defect at their beta-globin genes, remain unexplained.