Unusually Severe Heterozygous β-Thalassemia: Evidence for an Interacting Gene Affecting Globin Translation

摘要: A common β-thalassemia mutation in Asian populations is the C → T substitution at position 654 of intron 2, which leads to activation two cryptic splicing sites and incorporation 73 extra nucleotides into mutant mRNA. Like most mutations, it normally exhibits recessive inheritance. We investigated unusually severe phenotype heterozygotes for this mutation, father son, who had thalassemia intermedia an apparent dominant mode An increased level aberrantly spliced transcript reticulocytes probands compared with asymptomatic β654heterozygotes led us investigate production processing β654 RNA. showed that large amounts aberrant were detectable erythroblasts from one cases. The translation product mRNA was not vivo, we unable demonstrate a cell-free system. Although reticulocyte :β ratios within range observed heterozygotes, globin chain biosynthesis studies considerably greater imbalance. These results imply more may be due second defect, possibly unlinked β-globin cluster, acts translational or posttranslational level. © 1998 by American Society Hematology.