A novel mutation in the TATA box in a Japanese patient with ß+-thalassemia

Abstract

A single base substitution (A-G) at position -31 within the highly conserved proximal promoter element, the TATA box, was identified in the ß-globin gene cloned from a Japanese woman with ß+-thalassemia. It appears that she is homozygous for this specific allele, as determined by haplotype analysis using seven different polymorphic sites in the ß-globin gene cluster. Transient expression of the mutant gene in COS cells revealed a 45% reduction in ß-globin RNA production, relative to normal. These results establish the functional significance of the second base of the TATA box for in vivo transcription of the human ß-globin gene.