Unexpected pattern of beta-globin mutations in beta-thalassaemia patients from northern Portugal

We characterized the genetic nature of beta-thalassaemia in northern Portug al. Of the 164 patients studied three were beta-thalassaemia major cases (o ne IVS-1-6/beta degrees 39 and two homozygous IVS-1-110). The analysis of t he frequency of each mutation in the families revealed that the codon 6(-A) mutation was unexpectedly frequent (40%) and associated with the beta-glob in haplotype E, and not with the usual European and North African CD6(-A) h aplotypes. In contrast, the frequency of IVS-1-6 (8%) and beta degrees 39 ( 19%) was found to be lower than in the rest of the country. The frequency o f all other mutations was similar to previous reports for central/southern Portugal. Six families carried none of the most frequent mutations in the Mediterrane an area. These families were studied by gene sequencing, revealing that thr ee families carried a previously described mutation (CD16 G-->A). The remai ning families carried previously unidentified mutations: one showed an 86 b p insertion in exon 2 (named HGSA) and two showed a deletion of a cytidine in codon 11 (CD11(-C)). The results, showing a high frequency (82%) of beta degrees mutations, stro ngly indicates that genetic counselling should be intensified as a means of preventing the spread of the severe mutations found.