Molecular characterization of a novel form of (A gamma delta beta)zero thalassemia deletion in a Chinese family

• Published in: Blood 1993-03, Vol.81 (6), p.1624-1629
• Main Authors: Zhang, J W, Song, W F, Zhao, Y J, Wu, G Y, Qiu, Z M, Wang, F N, Chen, S S, Stamatoyannopoulos, G
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Chromosome Mapping; Female; Fetal Hemoglobin - genetics; Gene Deletion; Globins - genetics; Humans; Male; Thalassemia - genetics
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V81.6.1624.1624

We have identified and molecularly characterized a novel deletion in the beta-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 A gamma, delta, and beta-globin genes. The 5' breakpoint of the deletion is located about 0.13 kb upstream from the A gamma-globin gene, whereas the 3' breakpoint is located about 66 kb downstream from the beta-globin gene, about 13 kb upstream from the breakpoint of the Chinese (A gamma delta beta)zero-thalassemia. Heterozygotes for this Yunnanese form of (A gamma delta beta)zero-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 Yunnanese and the Chinese (A gamma delta beta)zero-thalassemia mutants is compatible with the hypothesis that an enhancer element is located between the 3' breakpoints of these two mutants. Juxta-position to the G gamma gene of this element may be responsible for the efficient gamma-gene expression in the Yunnanese mutant.