title: QDPR gene mutation and clinical follow-up in Chinese patients with dihydropteridine reductase deficiency.
abstract: BACKGROUND
  This study aimed to investigate the mutation spectrum of the QDPR gene, to determine the effect of mutations on dihydropteridine reductase (DHPR) structure/function, to discuss the potential genotypephenotype correlation, and to evaluate the clinical outcome of Chinese patients after treatment.
  
  
  METHODS
  Nine DHPR-deficient patients were enrolled in this study and seven of them underwent neonatal screening. QDPR gene mutations were analyzed and confirmed by routine methods. The potential pathogenicity of missense variants was analyzed using Clustal X, PolyPhen program and Swiss-PDB Viewer 4.04_OSX software, respectively. The clinical outcomes of the patients were evaluated after long-term treatment.
  
  
  RESULTS
  In 10 mutations of the 9 patients, 4 were novel mutations (G20V, V86D, G130S and A175R), 4 were reported by us previously, and 2 known mutations were identified. R221X was a hotspot mutation (27.7%) in our patients. Eight missense mutations probably had damage to protein. Six patients in this series were treated with a good control of phenylalanine level. The height and weight of the patients were normal at the age of 4 months to 7.5 years. Four patients, who underwent a neonatal screening and were treated early, showed a normal mental development. In 2 patients diagnosed late, neurological symptoms were significantly improved.
  
  
  CONCLUSIONS
  The mutation spectrum of the QDPR gene is different in the Chinese population. Most mutations are related to severe phenotype. The determination of DHPR activity should be performed in patients with hyperphenylalaninemia. DHPR-deficient patients who were treated below the age of 2 months may have a near normal mental development.
authors.affiliation: Department of Pediatric Endocrinology and Genetic Metabolism and Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China.
authors.forename: De-Yun
authors.initials: DY
authors.lastname: Lu
authors.forename: Jun
authors.initials: J
authors.lastname: Ye
authors.forename: Lian-Shu
authors.initials: LS
authors.lastname: Han
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Qiu
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Zhang
authors.forename: Jian-De
authors.initials: JD
authors.lastname: Zhou
authors.forename: Pei-Zhong
authors.initials: PZ
authors.lastname: Bao
authors.forename: Ya-Fen
authors.initials: YF
authors.lastname: Zhang
authors.forename: Xue-Fan
authors.initials: XF
authors.lastname: Gu
mesh_terms: D044466:Asian People / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D004093:Dihydropteridine Reductase / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D015997:Neonatal Screening; D010641:Phenotype; D010661:Phenylketonurias / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D017354:Point Mutation; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D004093:Dihydropteridine Reductase