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

Abstract

We characterized the genetic nature of β-thalassaemia in northern Portugal. Of the 164 patients studied three were β-thalassaemia major cases (one IVS-1-6/β°39 and two homozygous IVS-1-110). The analysis of the frequency of each mutation in the families revealed that the codon 6(−A) mutation was unexpectedly frequent (40%) and associated with the β-globin haplotype E, and not with the usual European and North African CD6(−A) haplotypes. In contrast, the frequency of IVS-1-6 (8%) and β°39 (19%) was found to be lower than in the rest of the country. The frequency of all other mutations was similar to previous reports for central/southern Portugal. Six families carried none of the most frequent mutations in the Mediterranean area. These families were studied by gene sequencing, revealing that three families carried a previously described mutation (CD16 G → A). The remaining families carried previously unidentified mutations: one showed an 86 bp 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 β° mutations, strongly indicates that genetic counselling should be intensified as a means of preventing the spread of the severe mutations found.