title: Identification of three novel 6-pyruvoyl-tetrahydropterin synthase gene mutations (226C>T, IVS3+1G>A, 116-119delTGTT) in Chinese hyperphenylalaninemia caused by tetrahydrobiopterin synthesis deficiency.
abstract: The enzyme 6-Pyruvoyl-tetrahydropterin synthase (PTS) deficiency is the major cause of BH(4)-deficient HPA. The frequency of BH(4)-deficient HPA was estimated to be around 30% among Chinese HPA population in Taiwan, which is much higher than that in Caucasian population (1.5-2% of HPA). Approximately 86% of Chinese BH(4)-deficient HPA was found to be caused by PTS-deficiency. Seven mutations - namely R25G, N52S, V56M, V70D, P87S, D96N, and T106M - had been identified in Chinese PTS-deficient patients previously. In this study, five additional mutations in the PTS gene, namely 200C>T (T67M), 226C>T (L76F), IVS3+1G>A (K54X), 116-119delTGTT (K38X) and 169-171delGTG (V57del), were identified by PCR and DNA sequencing in Chinese PTS-deficient patients. The 116-119delTGTT introduces a frameshift stop after lysine of codon 38 (K38X). The G-to-A transition at the consensus sequence of splicing donor site of exon 3 (IVS3+1G>A) resulted in exon 3 skipping of the PTS transcript and caused a frameshift stop after lysine of codon 54 (K54X). The T67M and V57del mutations have been found in Caucasian PTS deficient patients, while the L76F, IVS3+1G>A, and K38X mutations are novel. None of 100 normal alleles screened was found to have the L76F substitution, which indicated that the L76F substitution is a mutation causing PTS deficiency. Hum Mutat 18:83, 2001.
authors: Institute of Genetics, National Yang-Ming University, Taipei, Taiwan.
authors: T T
authors: TT
authors: Liu
authors: Y H
authors: YH
authors: Chang
authors: S H
authors: SH
authors: Chiang
authors: Y L
authors: YL
authors: Yang
authors: W M
authors: WM
authors: Yu
authors: K J
authors: KJ
authors: Hsiao
mesh_terms: D000483:Alleles; D017398:Alternative Splicing / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000172:deficiency*; D002681:China / Q000208:ethnology; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D010661:Phenylketonurias / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D019761:Phosphorus-Oxygen Lyases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D022821:RNA Splice Sites / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D013624:Taiwan; D044465:White People / Q000235:genetics
chemical_list: D022821:RNA Splice Sites; D012333:RNA, Messenger; D001708:Biopterins; D019761:Phosphorus-Oxygen Lyases; C043497:6-pyruvoyltetrahydropterin synthase; C003402:sapropterin