HAPLOTYPE ANALYSIS OF COMMON TRANSTHYRETIN MUTATIONS

The most frequent transthyretin (TTR) variant associated with heredita ry amyloidosis is TTR Met 30, which has its major focus in Portugal, a lthough it also occurs in many other countries, The distribution of th e mutation and its occurrence in a CpG dinucleotide lead us to questio n the origin of the mutation and the possibility of its having origina ted in Portugal. In order to investigate these questions, we studied t he distribution of haplotypes associated with the Met 30 mutation in f amilies from different European countries. All the analysed Portuguese families presented the same haplotype associated with the Met 30 muta tion (haplotype I). The same was found for the Swedish and Spanish fam ilies studied, However, a distinct haplotype (haplotype III) was found in three families, one Italian, one English and one Turkish. These re sults suggest that, although the Portuguese Met 30 carriers might have one founder, the mutation probably recurred in populations in Europe in a similar manner to that reported in Japan. In this study, we have also analysed the haplotypes associated with other TTR variants freque nt in the Portuguese population.