title: [Mutation analysis and one novel mutation detection of 6-pyruvoyl tetrahydropterin synthase gene in children with tetrahydrobiopterin deficiency].
abstract: OBJECTIVE
  To investigate the distribution character of the mutations of 6-pyruvoyl tetrahydropterin synthase (PTPS) gene and to provide effective basis for gene diagnosis of tetrahydrobiopterin deficiency (BH4D) in children with hyperphenylalaninemia.
  
  
  METHODS
  Direct sequencing was performed for screening the PTPS gene mutations in 5 patients with clinically suspected BH4D and their parents. The nature of the novel mutations were deduced by the sequences alignment and the structural analysis of mutant protein. Artificial construct restriction site was used to detect the novel mutation in the control samples. The dates of urinary pterin analysis and BH4 loading test were retrospectively analyzed after gene analysis.
  
  
  RESULTS
  Four PTPS gene mutations (N52S, P87S, D96N, and L127F) were detected in our study. The genotypes of four PTPS deficiency patients were identified as N52S/L127F, P87S/D96N, N52S/D96N, and D96N/ -. As a novel mutation that has not been reported previously, the mutation L127F was not detected in 50 normal controls. This novel mutation L127F was inherited from the patient's mother, and this mutant site was highly conserved by sequences alignment and the protein structural analysis. Four of the five cases with hyperphenylalaninemia and suspicious BH4D, whose urinary biopterin percentage was lower than 2% , were diagnosed as PTPS deficiency during 5-20 months old. The remaining one case was excluded from BH4D.
  
  
  CONCLUSIONS
  The mutant characterization of PTPS gene was coincident with other early studies in Chinese. The novel mutation L127F was considered as a pathogenetic mutation and associated with severe clinical phenotype.
authors.affiliation: Department of Medical Genetics, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Yu-Jin
authors.initials: YJ
authors.lastname: Qu
authors.forename: Fang
authors.initials: F
authors.lastname: Song
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Jin
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
mesh_terms: D044466:Asian People / Q000235:genetics; D001708:Biopterins / Q000031:analogs & derivatives* / Q000172:deficiency / Q000235:genetics; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009154:Mutation / Q000235:genetics*; D010661:Phenylketonurias / Q000235:genetics; D019761:Phosphorus-Oxygen Lyases / Q000235:genetics*; D016133:Polymerase Chain Reaction
chemical_list: D001708:Biopterins; D019761:Phosphorus-Oxygen Lyases; C043497:6-pyruvoyltetrahydropterin synthase; C003402:sapropterin