A KOREAN FAMILY WITH A DOMINANTLY INHERITED β-THALASSEMIA DUE TO Hb DURHAM-N.C./BRESCIA [β114(G16)Leu→Pro]

Abstract

We describe the molecular and the hematological characteristics of a Korean family with a dominantly inherited β-thalassemia. Carriers were characterized by moderate anemia, hypochromia, microcytosis, elevated Hb A₂ and Hb F levels, and splenomegaly. DNA analysis revealed a CTG (Leu) to CCG (Pro) substitution at codon 114 of the β-globin gene, that leads to a highly unstable hemoglobin variant, Hb Durham-N.C./Brescia, and this was linked to the β haplotype V, [+−−−−+−], and framework 2. RNA analysis showed that the proband had comparable levels of mutant and normal β-mRNA. Translation of the mutant mRNA would give rise to non-functional hyperunstable β-globin chains, and their degradation would, by placing an additional burden on the proteolytic process of the red blood cell precursors, result in a more severe phenotype.