EVIDENCE IN LATIN-AMERICA OF RECURRENCE OF V388M, A PHENYLKETONURIA MUTATION WITH HIGH IN-VITRO RESIDUAL ACTIVITY

Phenylketonuria mutation V388M is frequent in the Iberian Peninsula. I n vitro, the V388M mutant enzyme has similar immunoreactive protein an d phenylalanine hydroxylase mRNA and has 43% residual activity, which correlates well with the mild phenotype exhibited by the homozygous pa tients. In Spain it has been detected in 5.7% of the mutant alleles an d is always associated with haplotype 1.7. This mutation is also prese nt in high frequency in some Latin American countries (Brazil, 9%; Chi le, 13%). It is interesting that in Chile most of the alleles bearing this mutation carry haplotype 4.3, although in Brazil it is found only on the background of haplotype 1.7. The origin of V388M in Spain on h aplotype 1.7 and in Chile on haplotype 4.3 is clearly different. Recur rence is the most plausible explanation, because the mutation involves a CpG dinucleotide, and a recombination event transferring the mutati on from haplotype 1 to 4 is unlikely.