Common origin of the Val30Met mutation responsible for the amyloidogenic transthyretin type of familial amyloidotic polyneuropathy

Key pointsN Our work aimed to identify the origin of Val30Met mutation, responsible for the amyloidogenic transthyretin (TTR) type of familial amyloidotic polyneuropathy (FAP) found in Japan and Europe as foci.N We analysed the TTR gene haplotype of FAP patients from Japan, Portugal, Spain, and Sweden, and of Japanese and Caucasian control subjects with four single nucleotide polymorphisms (SNPs) and five microsatellite markers in the neighbouring gene region, spanning 215 kb (loci 1-9). NWe observed that the disease-causing haplotype is the same in two major foci in Japan, indicating the existence of a common founder.N By comparing haplotype among foci, we obtained results indicating that there could be a common founder for Japanese and Portuguese patients, and for Portuguese and Spanish patients, but not for Swedish or other patients.N These data, plus the history of 16th century trade, lead to the plausible hypothesis of a mutant allele of a Portuguese kindred being the origin of the mutation in most Japanese FAP patients.