Molecular heterogeneity of beta thalassaemia in the Italian population

Summary Fifty‐one subjects originating from Southern Italy and affected by Cooley's anaemia have been studied in order to define the degree of heterogeneity of β thalassaemia mutations in this high incidence area. Restriction endonuclease mapping has been carried out on genomic DNA by the Southern blot technique both to exclude the existence of gross deletions or rearrangements and to establish the relative frequency of four polymorphic restriction sites (i.e. Gγ and Aγ Hind III, β Ava II and β Bam HI) within the γδβ gene region. In 28 subjects unequivocal linkage of the four polymorphic sites has been determined leading to the identification of seven different chromosome haplotypes, six of which had previously been reported associated with specific β0 and β+ thalassaemia mutations. Globin chain synthesis studies on peripheral blood reticulocytes indicated that subjects carrying the same genotype may behave differently as far as the β chain production is concerned relative to both the a and the non‐α chains. Thus, β thalassaemia turns out to be quite heterogeneous even in this limited geographical area. β+ mutations appear to be predominant, particularly those affecting nuclear precursor RNA splicing to mature β globin mRNA. Copyright © 1984, Wiley Blackwell. All rights reserved