HOMOZYGOUS BETA-THALASSEMIA RESULTING IN THE BETA-THALASSEMIA CARRIERSTATE PHENOTYPE

This paper describes the phenotypic manifestations of a very mild beta -thalassaemia mutation detected in several members of two families of Italian descent. The molecular defect, defined by denaturing gradient gel electrophoresis analysis and direct sequencing, consists of a C -- > G substitution at position 844 of IVSII of the beta-globin gene with in the consensus sequence of the IVSII acceptor splice site. Heterozyg otes for this mutation show a haematological phenotype ranging in seve rity from silent beta-thalassaemia to that of a mild beta-thalassaemia carrier state, whereas homozygotes have the typical manifestations co mmonly resulting from heterozygosity for a beta-thalassaemia mutation. Compound heterozygotes for the IVSII nt844 (C --> G) mutation and a s evere beta-thalassaemia mutation have the phenotype of thalassaemia in termedia. This paper indicates that the presence of borderline red blo od cell indices or HbA(2) values should make one suspect the presence of a very mild or silent beta-thalassaemia.