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Pediatr Res. 2015 Dec;78(6):691-9. doi: 10.1038/pr.2015.167. Epub 2015 Aug 31.

Correlation between genotype and the tetrahydrobiopterin-responsive phenotype in Chinese patients with phenylketonuria.

Tao J1,2, Li N1,3, Jia H4, Liu Z1,3, Li X1,3, Song J4, Deng Y1,3, Jin X1,3, Zhu J1.

Author information

1
National Centre for Birth Defect Monitoring, West China Second University Hospital, Sichuan University, Sichuan, China.
2
West China School of Public Health, Sichuan University, Sichuan, China.
3
Laboratory of Molecular Epidemiology for Birth Defects, West China Second University Hospital, Sichuan University, Sichuan, China.
4
BGI-Shenzhen, Shenzhen, Guangdong, China.

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.

CONCLUSION:

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.

PMID:
26322415
PMCID:
PMC4700046
DOI:
10.1038/pr.2015.167
[Indexed for MEDLINE]
Free PMC Article

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