The β-globin promoter-71 C>T mutation is a β plus thalassemic allele

A novel beta-globin gene promoter (-71 C>T) nucleotide change was recently posted to the HbVar database (ID 2701) without precision on phenotype and ethnicity. We found the same change in compound heterozygosity with Hb S [beta 6(A3)Glu>Val] in an Omani family with almost equal expression of Hb A and Hb S. This suggested that the -71 C to T mutation may be a mild beta-thalassemic allele. Subsequent search found three other independent cases with the same atypical Hb A: Hb S ratio, further confirming the mild thalassemic feature of this mutation. In addition, molecular screening of a set of subjects (with only Hb A) with borderline Hb A(2) or MCV values revealed the presence of -71 C>T change in heterozygous state, altogether assigning the mutation as a mild beta(+) thalassemic allele. In a region such as Oman, where several genetic conditions of the red blood cell coexist (alpha- and beta-thalassemia, Hb S, Hb D, Hb E) in significant frequencies, it is crucial to decipher the molecular basis of these atypical forms of beta(+) thalassemias, especially in a genetic counseling setting.