Mild β⁺(−87)‐thalassemia CACCC box mutation is associated with elevated fetal hemoglobin expression in cis

Abstract

The beta zero-thalassemia codon 39 nonsense mutation predominant in Sardinia is severe, and homozygotes are transfusion dependent. Two-thirds of beta zero 39 alleles are linked to A gamma T (haplotype II). One-fourth are linked to A gamma I (haplotypes I and IX), as is the mild beta +-thalassemia -87 C-->G mutation (haplotype VIII). beta +/beta zero-Thalassemia VIII/II compound heterozygotes have significantly higher A gamma I:A gamma T (23:7) than beta zero-thalassemia I/II (24:20) or IX/II (16:17) cases. This suggests that the beta + -87 mutation is associated with elevated gamma expression in cis, which may contribute to the lack of transfusion-dependence in beta +/beta zero cases.