Homozygous β+ thalassaemia owing to a mutation in the cleavage-polyadenylation sequence of the human β globin gene

Abstract

A mild, non-transfusion dependent, β thalassaemia phenotype is described in a Dutch patient homozygous for a mutation in the cleavage-polyadenylation sequence of the β globin gene. The molecular basis of the mutation, AATAAA>AATGAA, was determined using denaturing gradient gel electrophoresis (DGGE) and direct sequencing of genomic DNA amplified by the polymerase chain reaction (PCR). Different fragments of the β globin gene were amplified and analysed on DGGE for the presence of mutations. The fragment with an abnormal melting behaviour was reamplified and the base substitution in the polyadenylation sequence was identified by direct sequencing.