Genetic and Biochemical Heterogeneity of β-Thalassaemia in Naples

S ummary We have investigated 32 children with Cooley's anaemia from Naples, Italy. Criteria for inclusion in the study were: (a) typical clinical and haematological findings; (b) absolute transfusion requirement; and (c) elevated Hb A₂ in both parents. From biosynthetic studies we have established that five children (including two sets of sibs) had β° thalassaemia, while the rest had β⁺ thalassaemia. Thus, the frequency of β⁺ thalassaemia among unrelated patients was about 90%. The distribution of β/α ratios among β⁺ patients ranged from 0·01 to 0·16 and it was bimodal, consistent with some of them having a β°/β⁺ genotype and others a β⁺/β⁺ genotype. The distribution of β/α ratios of the patients' parents (obligate heterozygotes) ranged from 0·24 to 0·73, and it was plurimodal, consistent with the coexistence in this population of multiple β thalassaemia alleles, of which one must be β° and at least one is β⁺. A systematic analysis of 20 families indicates that the β/α ratio is to some extent quantitatively inherited, and its suggests non-randomness in the assortment of β thalassaemia alleles that can give rise to a Cooley's phenotype.