A distant gene deletion affects β-globin gene function in an atypical γδβ-thalassemia

Abstract

We describe an English family with an atypical γδβ-thalassemia syndrome. Heterozygosity results in an β-thalassemia phenotype with normal hemoglobin A2. However, unlike previously described cases, no history of neonatal hemolytic anemia requiring blood transfusion was obtained. Gene mapping showed a deletion that extended from the third exon of the (Gγ)-globin gene upstream for ~100 kilobases (kb). The (Aγ)-globin, ψβ-, δ-, and β-globin genes in cis remained intact. The malfunction of the β-globin gene on chromosome in which the deletion is located 25 kb away suggests that chromatin structure and conformation are important for globin gene expression.