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. 2017 Oct 5;18(1):108.
doi: 10.1186/s12881-017-0467-7.

Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern China

Ning Liu  1 , Qiuying Huang  2 , Qingge Li  2 , Dehua Zhao  3 , Xiaole Li  3 , Lixia Cui  4 , Ying Bai  1 , Yin Feng  1 , Xiangdong Kong  5
Affiliations

Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern China

Ning Liu et al. BMC Med Genet. .

Erratum in

Abstract

Background: Phenylketonuria (PKU), which primarily results from a deficiency of phenylalanine hydroxylase (PAH), is one of the most common inherited inborn errors of metabolism that impairs postnatal cognitive development. The incidence of various PAH variations differs by race and ethnicity. The aim of the present study was to characterize the PAH gene variants of a Han population from Northern China.

Methods: In total, 655 PKU patients and their families were recruited for this study; each proband was diagnosed both clinically and biochemically with phenylketonuria. Subjects were sequentially screened for single-base variants and exon deletions or duplications within PAH via direct Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA).

Results: A spectrum of 174 distinct PAH variants was identified: 152 previously documented variants and 22 novel variants. While single-base variants were distributed throughout the 13 exons, they were particularly concentrated in exons 7 (33.3%), 11 (14.2%), 6 (13.2%), 12 (11.0%), 3 (10.4%), and 5 (4.4%). The predominant variant was p.Arg243Gln (17.7%), followed by Ex6-96A > G (8.3%), p.Val399 = (6.4%), p.Arg53His (4.7%), p.Tyr356* (4.7%), p.Arg241Cys (4.6%), p.Arg413Pro (4.6%), p.Arg111* (4.4%), and c.442-1G > A (3.4%). Notably, two patients were also identified as carrying de novo variants.

Conclusion: The composition of PAH gene variants in this Han population from Northern China was distinct from those of other ethnic groups. As such, the construction of a PAH gene variant database for Northern China is necessary to lay a foundation for genetic-based diagnoses, prenatal diagnoses, and population screening.

Keywords: MLPA; PAH gene variant; Phenylalanine hydroxylase gene; Phenylketonuria.

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Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University, and was performed according to the principles of the Declaration of Helsinki. All subjects or guardians provided signed informed consent.

Consent for publication

All subjects or guardians have signed informed consent to participate in this study and allowed us publish the result of study.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flow chart depicting the strategy used for gene diagnosis in hyperphenylalaninemia patients
See this image and copyright information in PMC

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