Phenylketonuria mutations in Europe

Hum Mutat. 2003 Apr;21(4):345-56. doi: 10.1002/humu.10192.


Phenylketonuria (PKU) is heterogeneous. More than 400 different mutations in the phenylalanine hydroxylase (PAH) gene have been identified. In a systematic review of the molecular genetics of PKU in Europe we identified 29 mutations that may be regarded as prevalent in European populations. Comprehensive regional data for these mutations were collated from all available studies. The spectrum of mutations found in individual regions results from a combination of factors including founder effect, range expansion and migration, genetic drift, and probably heterozygote advantage. Common mutations include R408W on a haplotype 2 background in Eastern Europe, IVS10-11G>A in the Mediterranean, IVS12+1G>A in Denmark and England, Y414C in Scandinavia, I65T in Western Europe, and R408W on haplotype 1 in the British Isles. Molecular data from mild hyperphenylalaninemia (MHP) patients are available from a number of countries, but it is currently not possible to calculate relative allele frequencies. The available data on PAH mutations are useful for the understanding of both the clinical features and the population genetics of PAH deficiency in Europe.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Europe / epidemiology
  • Genetics, Population
  • Humans
  • Mutation / genetics*
  • Phenylketonurias / epidemiology
  • Phenylketonurias / genetics*