title: Mutation spectrum of and founder effects affecting the PTS gene in East Asian populations.
abstract: The enzyme 6-pyruvoyl-tetrahydropterin synthase (PTPS, gene symbol: PTS) is involved in the second step of the de novo biosynthesis of tetrahydrobiopterin (BH4), which is a vital cofactor of nitric oxide synthases and three types of aromatic amino acid hydroxylases; the latter are important enzymes in the production of neurotransmitters. We conducted a study of PTS mutations in East Asia, including Taiwan, Mainland China, Japan, South Korea, the Philippines, Thailand and Malaysia. A total of 43 mutations were identified, comprising 22 previously reported mutations and 21 new discovered mutations. Among these, the c.155A>G, c.259C>T, c. 272A>G, c.286G>A and c.84-291A>G mutations were the most common PTS mutations in East Asia, while the c.58T>C and c.243G>A mutations were, respectively, specific to Filipinos and Japanese originating from Okinawa. Further studies demonstrated that each of the mutations listed above was in linkage disequilibrium to a specific allele of polymorphic microsatellite marker, D11S1347. These results suggest the presence of founder effects that have affected these frequent mutations in East Asia populations. In this context, D11S1347 should become one of the most reliable polymorphic markers for use in prenatal diagnosis among PTPS deficient families, especially where mutations are yet to be identified.
authors.affiliation: Institute of Genetics, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yen-Hui
authors.initials: YH
authors.lastname: Chiu
authors.forename: Ying-Chen
authors.initials: YC
authors.lastname: Chang
authors.forename: Yu-Hsin
authors.initials: YH
authors.lastname: Chang
authors.forename: Dau-Ming
authors.initials: DM
authors.lastname: Niu
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Ye
authors.forename: Jianhui
authors.initials: J
authors.lastname: Jiang
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Okano
authors.forename: Dong Hwan
authors.initials: DH
authors.lastname: Lee
authors.forename: Suthipong
authors.initials: S
authors.lastname: Pangkanon
authors.forename: Chulaluck
authors.initials: C
authors.lastname: Kuptanon
authors.forename: Ngu Lock
authors.initials: NL
authors.lastname: Hock
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Chiong
authors.forename: Barbra V
authors.initials: BV
authors.lastname: Cavan
authors.forename: Kwang-Jen
authors.initials: KJ
authors.lastname: Hsiao
authors.forename: Tze-Tze
authors.initials: TT
authors.lastname: Liu
mesh_terms: D017398:Alternative Splicing; D044466:Asian People; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005202:Asia, Eastern; D018703:Founder Effect; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D019761:Phosphorus-Oxygen Lyases / Q000172:deficiency / Q000235:genetics*; D017354:Point Mutation; D011296:Prenatal Diagnosis
chemical_list: D019761:Phosphorus-Oxygen Lyases; C043497:6-pyruvoyltetrahydropterin synthase