An Initiation Codon Mutation as a Cause of a β-Thalassemia

Abstract

During the course of a screening program for β-thalassemia mutations among p-thalassemia heterozygotes in Yugoslavia we observed a mutation (ATG-ACG) in the initiation codon of the B-globin gene which has not been described before. The abnormality was initially detected through mapping of the β-globin gene by Southern blot analysis using the restriction enzyme Nco I. The loss of the Nco I site resulted in the presence of an 8.3 kb band in addition to the normal 5.2 kb band. The mutation was identified by sequence analysis of amplified DNA and by dot-blot analysis of this DNA with a ³²P-labeled oligonucleotide probe. An additional polymorphism (CAC + CAT) was present at codon 2 on the same chromosome; this mutation was detected by Orkin et al in 1982 (1). Hematological and _in_ vitro chain synthesis data suggest that the β-thalassemia is of the β type.