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

Pediatric Research
Jing TaoJun Zhu

Abstract

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. 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. 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. 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.

References

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Citations

Feb 27, 2016·Human Mutation·Nenad Blau
Oct 17, 2017·Journal of Pediatric Endocrinology & Metabolism : JPEM·Rihwa ChoiDong Hwan Lee
Apr 4, 2021·International Journal of Neonatal Screening·Shino OdagiriTakashi Hamazaki

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Datasets Mentioned

BETA
AY260740

Methods Mentioned

BETA
PCR
chip
electrophoresis

Software Mentioned

SIFT Blink
SNPs3D
Exome Variant Server
PolyPhen

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