MILD BETA+(-87)-THALASSEMIA CACCC BOX MUTATION IS ASSOCIATED WITH ELEVATED FETAL HEMOGLOBIN EXPRESSION IN CIS

The beta degrees-thalassemia codon 39 nonsense mutation predominant in Sardinia is severe, and homozygotes are transfusion dependent. Two-thirds of beta degrees 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 degrees-Thalassemia VII/VII compound heterozygotes have significantly higher (A) gamma(I):(A) gamma(T) (23:7) than beta degrees-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 degrees cases. (C) 1994 Wiley-Liss, Inc.