Lr. Desviat et al., EVIDENCE IN LATIN-AMERICA OF RECURRENCE OF V388M, A PHENYLKETONURIA MUTATION WITH HIGH IN-VITRO RESIDUAL ACTIVITY, American journal of human genetics, 57(2), 1995, pp. 337-342
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.