Clinical expression of a rare beta-globin gene mutation co-inherited with haemoglobin E-disease

A single nucleotide substitution and the effect on the phenotype in an Indonesian family with beta-thalassaemia, HbE-trait and HbE-beta-thalassaemia is described. In the proposita (female, age 20 (Hb 7.4 mmol/l; MCV 72 fl; MCH 1.45 fmol; HbA2 3.5%; HbF 2.4%)). An A/G mutation in the RNA cleavage and polyadenylation sequence was detected (AATAAA/AATAGA). Her sister (Hb 8.2 mmol/l; MCV 77 fl; MCH 1.60 fmol; HbA2/HbE 32.4%), carried a different mutation in the beta-globin gene (codon 25; G129/A), and consequently had HbE-trait. Their mother had a haemoglobin concentration of 6.4 mmol/l (MCV 56 fl; MCH 1.20 fmol; HbA2/HbE 55.8%). She was compound heterozygous for the mutation in the poly A-signal and HbE-trait. Using restriction enzyme analysis and linkage studies, we subsequently identified six family members with HbE-beta-thalassaemia, five with beta-thalassaemia and six with HbE-trait. Two individuals were unaffected. The mutation in the polyadenylation sequence causes a mild form of beta (+)-thalassaemia. The MCV and MCH in individuals with both beta-thalassaemia and HbE-trait were significantly lower, yet on average they were only slightly more anaemic than those carrying only the thalassaemic gene.