title: The mutation spectrum of the phenylalanine hydroxylase (PAH) gene and associated haplotypes reveal ethnic heterogeneity in the Taiwanese population.
abstract: 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.
authors.affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Miao-Zeng
authors.initials: MZ
authors.lastname: Huang
authors.affiliation: Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Cheng-Yi
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Hung-Kun
authors.initials: HK
authors.lastname: Chao
authors.affiliation: Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Victor Tramjay
authors.initials: VT
authors.lastname: Fwu
authors.affiliation: Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Szu-Hui
authors.initials: SH
authors.lastname: Chiang
authors.affiliation: Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Kwang-Jen
authors.initials: KJ
authors.lastname: Hsiao
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Dau-Ming
authors.initials: DM
authors.lastname: Niu
authors.affiliation: 1] Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan [2] Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Tsung-Sheng
authors.initials: TS
authors.lastname: Su
mesh_terms: D005006:Ethnicity / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D013624:Taiwan
chemical_list: D010651:Phenylalanine Hydroxylase