title: Correlation between genotype and the tetrahydrobiopterin-responsive phenotype in Chinese patients with phenylketonuria.
abstract: BACKGROUND
  A growing body of research has suggested that tetrahydrobiopterin (BH4) responsive phenotype can be predicted by the phenylalanine hydroxylase (PAH) genotype in patients with phenylketonuria (PKU), but data concerning the association between genotype and BH4 responsiveness are scarce in China.
  
  
  METHODS
  A total of 165 PKU patients from China who had undergone a 24-h loading test with BH4 administration were recruited. Genotyping was performed by the next-generation sequencing (NGS) technique. Using the predicted residual PAH activity, we analyzed the association between genotype and BH4-responsiveness.
  
  
  RESULTS
  Among the 165 patients, 40 patients (24.24%) responded to BH4. A total of 74 distinct mutations were observed, including 13 novel mutations. The mutation p.R241C was most frequently associated with response. Two known mutations (p.A322T and p.Q419R) and two novel mutations (p.L98V and IVS3-2A>T) were first reported as responsive to BH4. Residual PAH activity of at least 12.5% was needed for responsive genotypes.
  
  
  CONCLUSIONS
  Genotype-based predictions of BH4-responsiveness are only for selecting potential responders. Accordingly, it is necessary to test potential responders with a long-term BH4 challenge.
authors: National Centre for Birth Defect Monitoring, West China Second University Hospital, Sichuan University, Sichuan, China.|West China School of Public Health, Sichuan University, Sichuan, China.
authors: Jing
authors: http://orcid.org/0000-0003-3512-7645
authors: J
authors: Tao
authors: National Centre for Birth Defect Monitoring, West China Second University Hospital, Sichuan University, Sichuan, China.|Laboratory of Molecular Epidemiology for Birth Defects, West China Second University Hospital, Sichuan University, Sichuan, China.
authors: Nana
authors: N
authors: Li
authors: BGI-Shenzhen, Shenzhen, Guangdong, China.
authors: Haitao
authors: H
authors: Jia
authors: National Centre for Birth Defect Monitoring, West China Second University Hospital, Sichuan University, Sichuan, China.|Laboratory of Molecular Epidemiology for Birth Defects, West China Second University Hospital, Sichuan University, Sichuan, China.
authors: Zhen
authors: Z
authors: Liu
authors: National Centre for Birth Defect Monitoring, West China Second University Hospital, Sichuan University, Sichuan, China.|Laboratory of Molecular Epidemiology for Birth Defects, West China Second University Hospital, Sichuan University, Sichuan, China.
authors: Xiaohong
authors: X
authors: Li
authors: BGI-Shenzhen, Shenzhen, Guangdong, China.
authors: Jiaping
authors: J
authors: Song
authors: National Centre for Birth Defect Monitoring, West China Second University Hospital, Sichuan University, Sichuan, China.|Laboratory of Molecular Epidemiology for Birth Defects, West China Second University Hospital, Sichuan University, Sichuan, China.
authors: Ying
authors: Y
authors: Deng
authors: National Centre for Birth Defect Monitoring, West China Second University Hospital, Sichuan University, Sichuan, China.|Laboratory of Molecular Epidemiology for Birth Defects, West China Second University Hospital, Sichuan University, Sichuan, China.
authors: Xi
authors: X
authors: Jin
authors: National Centre for Birth Defect Monitoring, West China Second University Hospital, Sichuan University, Sichuan, China.
authors: Jun
authors: J
authors: Zhu
mesh_terms: D044466:Asian People / Q000235:genetics; D001708:Biopterins / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002681:China; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D010641:Phenotype; D010651:Phenylalanine Hydroxylase / Q000235:genetics* / Q000378:metabolism; D010661:Phenylketonurias / Q000175:diagnosis / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D011237:Predictive Value of Tests
chemical_list: D001708:Biopterins; D010651:Phenylalanine Hydroxylase; C003402:sapropterin