CLINICAL EXPRESSION OF A RARE BETA-GLOBIN GENE MUTATION CO-INHERITED WITH HEMOGLOBIN E-DISEASE

A single nucleotide substitution and the effect on the phenotype in an Indonesian family with beta-thalassaemia, HbE-trait and HbE-beta-thal assaemia is described. In the proposita (female, age 20 (Hb 7.4 mmol/l ; MCV 72 fl; MCH 1.45 fmol; HbA(2) 3.5%; HbF 2.4%)). an A/G mutation i n the RNA cleavage and polyadenylation sequence was detected (<AATA(A) under bar A>/<AATA(G)under bar A). Her sister (Hb 8.2 mmol/l; MCV 77 f l; MCH 1.60 fmol; HbA(2)/HbE 32.4%), carried a different mutation in t he beta-globin gene (codon 25; G(129)/A), and consequently had HbE-tra it. Their mother had a haemoglobin concentration of 6.4 mmol/l (MCV 56 fl; MCH 1.20 fmol; HbA(2)/HbE 55.8%). She was compound heterozygous f or the mutation in the poly A-signal and HbE-trait. Using restriction enzyme analysis and linkage studies, we subsequently identified six fa mily members with HbE-beta-thalassaemia, five with beta-thalassaemia a nd six with HbE-trait. Two individuals were unaffected. The mutation i n the polyadenylation sequence causes a mild form of beta(+)-thalassae mia. The MCV and MCH in individuals with both beta-thalassaemia and Hb E-trait were significantly lower, yet on average they were only slight ly more anaemic than those carrying only the thalassaemic gene.