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BMC Medical Genetics

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Open Access 01-12-2017 | Research article

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

Authors: Ning Liu, Qiuying Huang, Qingge Li, Dehua Zhao, Xiaole Li, Lixia Cui, Ying Bai, Yin Feng, Xiangdong Kong

Published in: BMC Medical Genetics | Issue 1/2017

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.

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Title: Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern China
Authors: Ning Liu
Qiuying Huang
Qingge Li
Dehua Zhao
Xiaole Li
Lixia Cui
Ying Bai
Yin Feng
Xiangdong Kong
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2017
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/s12881-017-0467-7

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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