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Mutational spectrum of phenylketonuria in Jiangsu province

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Abstract

Phenylketonuria (PKU) is caused by variants in the phenylalanine hydroxylase (PAH) gene. We systematically investigated all 13 exons of the PAH gene and their flanking introns in 31 unrelated patients and their parents using next-generation sequencing (NGS). A total of 33 different variants were identified in 58 of 62 mutant PAH alleles. The prevalent variants with a relative frequency of 5 % or more were c.721C > T, c.1068C > A, c.611A > G, c.1197A > T, c.728G > A, c.331C > T, and c.442-1G > A. One novel variant was identified in this study—c.699C > G. We studied genotype–phenotype correlations using the Guldberg arbitrary value (AV) system, which revealed a consistency rate of 38 % (8/21) among the 21 predicted phenotypes. The genotype-based prediction of BH4 responsiveness was also evaluated, and 14 patients (45.2 %) were predicted to be BH4 responsive.

Conclusion: This study presents the spectrum of PAH variants in Jiangsu province. The information obtained from the genotype-based prediction of BH4 responsiveness might be used for the rational selection of candidates for BH4 testing.

What is known:

• Phenylketonuria (PKU) is caused by variants in the phenylalanine hydroxylase (PAH) gene.

• The spectrum of PAH variants in different Chinese populations has been reported.

What is new:

• This is the first report on the spectrum of PAH variants in Jiangsu province.

• This study identified one novel PAH variant—c.699C>G—and and tries to show a genotype–phenotype relationship also regarding BH4-responsiveness.

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Abbreviations

PAH:

Phenylalanine hydroxylase

PKU:

Phenylketonuria

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Acknowledgments

The authors gratefully acknowledge the Foundation Program of the Jiangsu Province Department of Health (H201245) and the Science and Technology Support Program-Social Development of Science and Technology Bureau of Jiangsu Province (no. BE2012608) for their financial support.

Conflict of interest

The authors declare that they have no competing interests.

Ethical statement

This study was approved by the Institutional Review Board of Wuxi Maternal and Child Health Hospital. Written informed consent was obtained from all participants and, if younger than 18 years, their parents/guardians.

Authors’ contributions

Ya-fen Chen and Xin-ye Jiang conceived the study. Hai-tao Jia, Jing-jing Pei, Zhi-jun Wu, and Ya-li Qiu carried out sample and data acquisition and interpretation. Jia-ping Song, Jing Wang, Zhong-hai Chen, Gang Liu, and Dong-mei Sun analyzed the data and prepared the manuscript. Yu Liang provided intellectual input and helped in drafting the final manuscript. All authors provided intellectual contributions to the manuscript and has read and approved the final version.

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Authors and Affiliations

  1. Department of Children Health Care, Wuxi Maternal and Child Health Hospital, No.48 Huaishu Alley, Wuxi, Jiangsu Province, China

    Ya-fen Chen, Jing-jing Pei, Zhi-jun Wu & Xin-ye Jiang

  2. Beijing Genomics Institute at Shenzhen, Building No.11, Beishan Industrial Zone, Yantian District, Shenzhen, Guangdong, China

    Hai-tao Jia, Zhong-hai Chen, Jia-ping Song, Yu Liang, Gang Liu & Dong-mei Sun

  3. Department of Children Health Care, Suqian Maternal and Child Health Hospital, No. 9 Ping-An Road, Suqian, Jiangsu Province, China

    Jing Wang & Ya-li Qiu

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  1. Ya-fen Chen
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  9. Ya-li Qiu
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  10. Gang Liu
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  11. Dong-mei Sun
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  12. Xin-ye Jiang
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Corresponding author

Correspondence to Xin-ye Jiang.

Additional information

Communicated by Beat Steinmann

Revisions received: 18 March 2015/01 April 2015

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Cite this article

Chen, Yf., Jia, Ht., Chen, Zh. et al. Mutational spectrum of phenylketonuria in Jiangsu province. Eur J Pediatr 174, 1333–1338 (2015). https://doi.org/10.1007/s00431-015-2539-z

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  • DOI: https://doi.org/10.1007/s00431-015-2539-z

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