Thalassemia Intermedia : Moderate Reduction of fl Globin Gene Transcriptional Activity by a Novel Mutation of the Proximal CACCC Promoter Element

A patient with homozygous p thalassemia of Germadtalian descent was found to be doubly heterozygous for the common IVSI-110 G -+ A mutation of the p globin gene and for a novel C -+ T mutation of the proximal CACCC-box of the p globin gene promoter at position -87 relativeto the transcription start site (cap). Transcription analysis in an HeLa cell transfection assay indicated a 45% to 51% residual activity of the gene with the -87 C -+ T mutation relative to normal, further underlining the physiologic role of the affected promoter element. The finding of an only moderately reduced