Molecular characterization of a novel form of (Aγδβ)0 thalassemia deletion in a Chinese family

Abstract

We have identified and molecularly characterized a novel deletion in the β-globin gene cluster that is associated with elevated fetal hemoglobin in the adult. The propositus is a homozygote from the Yunnan province of China. The deletion spans about 90 kb of DNA and removes the Aγ,δ, and β-globin genes. The 5′ breakpoint of the deletion is located about 0.13 kb upstream from the Aγ-globin gene, whereas the 3′ breakpoint is located about 66 kb downstream from the β-globin gene, about 13 kb upstream from the breakpoint of the Chinese (Aγδβ)0-thalassemia. Heterozygotes for this Yunnanese form of (Aγδβ)0-thalassemia express between 9% and 17% of fetal hemoglobin, whereas the homozygote present with a mild anemia (Hb = 10.7 g/dl). Comparison of the sites of 3′ breakpoints of the Yunanese and the Chinese (Aγδβ)0-thalassemia mutants is compatible with the hypothesis that an enhancer element is located between the 3′ breakpoints of these two mutants. Juxtaposition to the Gγ gene of this element may be responsible for the efficient γ-gene expression in the Yunanese mutant. © 1993 by The American Society of Hematology.