Jamaican S beta(+)-thalassaemia: mutations and haematology

The sickling disorders are a common cause of morbidity and mortality in Jam aica. Sickle cell beta(+)-thalassaemia is the fourth commonest form, occurr ing in one in every 3000 births, This is a heterogeneous condition, produci ng HbS, HbF and HbA(2) with variable amounts of HbA, depending on the mutat ion and, within a defined population, only a few beta-thalassaemia mutation s occur at high frequency This study establishes the frequency of beta-thal assaemia mutations in S beta(+)-thalassaemia patients in Jamaica. In additi on, comparison of the haematological phenotypes is possible by looking at t he 'average steady-state haematology' of the different mutational groups. B lood samples from 132 unrelated S beta(+)-thalassaemia patients attending t he MRC Sickle Cell Unit at the University of the West Indies were analysed by amplification refractory mutation system (ARMS) polymerase chain reactio n (PCR) or sequencing to determine the nature and frequencies of the underl ying beta-thalassaemia mutations. Ten mutations were identified, four of wh ich accounted for 93% of patients studied. These were -29(A-->G) in 71 (54% ), -88(C-->T) in 27 (20%), poly(T-->C) in 17 (13%) and IVS1-5(G-->C) in nin e (7%). The six remaining mutations found at low frequency were C24(T-->A) in two patients and one each of IVS2-848(C-->A), -90(C-->T), IVS1-5(G-->T), IVS1-5(G-->A) and IVS1-6 (T-->C). In one individual, no mutation was found . The three commonest mutations were all associated with haemoglobin levels of greater than 10 g/dl, whereas IVS1-5 (G-->C) had a more severe haematol ogical phenotype, The predominance of -29(A-->G) and -88(C-->T) is in keepi ng with other studies on populations of African origin, IVS1-5(G-->C) is fo und chiefly in Indian populations, and all affected families acknowledged I ndian ancestry, reflecting the prominent Indian community in Jamaica.