A Korean family with a dominantly inherited beta-thalassemia due to Hb Durham-NC/Brescia [beta 114(G16)Leu -> Pro]

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