A Novel Intrachromosomal Rearrangement in the β-Globin Gene Fd in An African-American Family

We describe here a deletion of 34 nucleotides from the 3′ end of the first intervening sequence of the β-globin gene covering the AGGC splice junction, and the insertion of 32 nucleotides of the δ-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 father, and her two brothers, including the one who carried the β-globin gene rearrangement, were found to be heterozygous for a-thalassemia-2 (-α3.7). 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 β-globin genes. The discrepancies between the phenotypes and the globin chain synthesis ratios of the mother, her daughte...

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