Molecular heterogeneity of β-thalassaemia in the Japanese: identification of two novel mutations

Summary Five unrelated Japanese β-thalassaemia genes, from one homozygote and four heterozygotes, have been systematically characterized using DNA polymorphism analysis, polymerase chain reaction, dot-blot hybridization and direct sequencing of amplified genomic DNA. Four different molecular defects were observed on three different β-globin gene frameworks. One of these, the AG mutation in the TATA box, a previously described mutation, was detected by dot-blot hybridization in one homozygote and one heterozygote with the β-globin gene of framework 2. The second mutation is a CT substitution at position 654 of IVS-2, the mutation commonly found in Chinese, which was associated with the framework 1 gene. Another two mutations, both associated with framework 3 genes, are novel ones; an amber mutation in codon 90 (GAG to TAG) and a frameshift (+G) insertion in codon 54, both of which cause a β0-thalassaemia phenotype by premature termination of the β-globin chain synthesis.