Desviat L R, Pérez B, De Lucca M, Cornejo V, Schmidt B, Ugarte M
Centro de Biología Molecular Severo Ochoa CSIC-UAM, Universidad Autónoma de Madrid, Spain.
Am J Hum Genet. 1995 Aug;57(2):337-42.
Phenylketonuria mutation V388M is frequent in the Iberian Peninsula. In vitro, the V388M mutant enzyme has similar immunoreactive protein and phenylalanine hydroxylase mRNA and has 43% residual activity, which correlates well with the mild phenotype exhibited by the homozygous patients. In Spain it has been detected in 5.7% of the mutant alleles and is always associated with haplotype 1.7. This mutation is also present in high frequency in some Latin American countries (Brazil, 9%; Chile, 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 haplotype 1.7 and in Chile on haplotype 4.3 is clearly different. Recurrence is the most plausible explanation, because the mutation involves a CpG dinucleotide, and a recombination event transferring the mutation from haplotype 1 to 4 is unlikely.
苯丙酮尿症突变V388M在伊比利亚半岛较为常见。在体外，V388M突变酶具有相似的免疫反应性蛋白和苯丙氨酸羟化酶mRNA，且具有43%的残余活性，这与纯合患者表现出的轻度表型密切相关。在西班牙，已在5.7%的突变等位基因中检测到该突变，且总是与单倍型1.7相关。在一些拉丁美洲国家（巴西，9%；智利，13%）该突变也以高频率存在。有趣的是，在智利，大多数携带该突变的等位基因带有单倍型4.3，尽管在巴西仅在单倍型1.7的背景下发现该突变。西班牙单倍型1.7上的V388M和智利单倍型4.3上的V388M起源明显不同。重复发生是最合理的解释，因为该突变涉及一个CpG二核苷酸，并且一个将该突变从单倍型1转移到4的重组事件不太可能发生。
