The mutation spectrum of the phenylalanine hydroxylase (PAH) gene and associated haplotypes reveal ethnic heterogeneity in the Taiwanese population

J Hum Genet. 2014 Mar;59(3):145-52. doi: 10.1038/jhg.2013.136. Epub 2014 Jan 9.


Phenylalanine hydroxylase (PAH) deficiency is responsible for most cases of phenylketonuria (PKU). In this study of the PAH mutation spectrum in the Taiwanese population, 139 alleles were identified including 34 different mutations. The V190G, Q267R and F392I mutations are first reported in this study. The most common mutations, R241C, R408Q and Ex6-96A>G, account for 23.2%, 12.0% and 9.2%, of the mutant alleles, respectively. Haplotype analysis shows that R241C and Ex6-96A>G are exclusively associated with haplotype 4.3 to suggest founder effects. On the other hand, R408Q is found on two distinct haplotypes suggesting recurrent mutations. The spectrum of PAH mutations in Taiwan shows various links to those of other Asian regions, yet remarkable differences exist. Notably, R408Q, E286K and -4173_-407del, accounting for 21% of all mutant alleles in Taiwan, are very rare or are undetected among PKU cohorts of other Asian regions to suggest local founder effects. Moreover, the low homozygosity value of 0.092 hints at a high degree of ethnic heterogeneity within the Taiwanese population. Our study of PAH mutation spectrum and the associated haplotypes is useful for subsequent study on the origin and migration pattern via Taiwan, an island at the historical crossroad of migration of ancient populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ethnicity / genetics*
  • Gene Frequency / genetics
  • Genetic Association Studies
  • Genetic Heterogeneity*
  • Haplotypes / genetics*
  • Humans
  • Mutation / genetics*
  • Phenylalanine Hydroxylase / genetics*
  • Taiwan


  • Phenylalanine Hydroxylase