One base substitution in IVS-2 causes a beta +-thalassemia phenotype in a Chinese patient

Two beta-globin genes derived from a Chinese patient with a beta +-thalassemia phenotype have been cloned and sequenced. A four-nucleotide deletion in codon 41 and 42 was found in one of the clones and a C to T substitution at position 654 of IVS-2 was detected in the other clone. The former change, which causes premature termination at codon 59, was found previously in another Chinese patient with homozygous beta 0-thalassemia. The latter change, which has not been reported so far, creates a sequence much like the consensus sequence of the 5' splice site. These results suggest that the new base change found in IVS-2 causes aberrant splicing of the beta-globin mRNA precursor. Thus, this patient is doubly heterozygous for beta 0- and beta +-thalassemia.