title: Chromosomal localization, genomic structure and characterization of the human gene and a retropseudogene for 6-pyruvoyltetrahydropterin synthase.
abstract: Autosomal recessive mutations in the 6-pyruvoyltetrahydropterin synthase (PTPS) gene are the most common reason for hyperphenylalaninemia due to tetrahydrobiopterin deficiency. We used the previously isolated PTPS cDNA as a probe and identified the human gene, PTS, located on chromosome 11q22.3-q23.3, and a retropseudogene, PTS-P1, assigned to 9p12-p13 (symbols approved by the human genome nomenclature committee). PTS-P1 has 74% similarity to the 3' portion of PTPS cDNA. The PTS gene spans about 8 kb and consists of 6 exons, as revealed by DNA-sequence analysis. This gene structure differs from that published previously which was reported to contain only two exons [Ashida, A., Owada, M. & Hatakeyama, K. (1994) Genomics 24,408-410]. By means of intron-specific primers, we amplified exon 3 from genomic DNA of a PTPS-deficient patient and found a mutation in the 3' acceptor splice site, which is responsible for skipping of exon 3.
authors.affiliation: Department of Pediatrics, University of Zürich, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Kluge
authors.forename: L
authors.initials: L
authors.lastname: Brecevic
authors.forename: C W
authors.initials: CW
authors.lastname: Heizmann
authors.forename: N
authors.initials: N
authors.lastname: Blau
authors.forename: B
authors.initials: B
authors.lastname: Thöny
mesh_terms: D000429:Alcohol Oxidoreductases / Q000737:chemistry / Q000172:deficiency / Q000235:genetics*; D017398:Alternative Splicing / Q000235:genetics; D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D003001:Cloning, Molecular; D005091:Exons / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D010649:Phenylalanine / Q000097:blood; D019761:Phosphorus-Oxygen Lyases; D017421:Sequence Analysis
chemical_list: D010649:Phenylalanine; D000429:Alcohol Oxidoreductases; D019761:Phosphorus-Oxygen Lyases; C043497:6-pyruvoyltetrahydropterin synthase