Mutation analysis of the PAH gene in children with phenylketonuria from the Qinghai area of China

HE Jiang; WANG Hui-Zhen; XU Fa-Liang; YANG Xi; WANG Rui; ZOU Hong-Yun; YU Wu-Zhong

doi:10.7499/j.issn.1008-8830.2015.11.014

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Chinese Journal of Contemporary Pediatrics ›› 2015, Vol. 17 ›› Issue (11) : 1221-1227. DOI: 10.7499/j.issn.1008-8830.2015.11.014

CLINICAL RESEARCH

Mutation analysis of the PAH gene in children with phenylketonuria from the Qinghai area of China

HE Jiang¹, WANG Hui-Zhen², XU Fa-Liang², YANG Xi¹, WANG Rui¹, ZOU Hong-Yun¹, YU Wu-Zhong¹

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Abstract

Objective To study the mutation characteristics of the phenylalanine hydroxylase (PAH) gene in children with phenylketonuria (PKU) from the Qinghai area of China, in order to provide basic information for genetic counseling and prenatal diagnosis. Methods Mutations of the PAH gene were detected in the promoter and exons 1-13 and their flanking intronic sequences of PAH gene by PCR and DNA sequencing in 49 children with PKU and their parents from the Qinghai area of China. Results A total of 30 different mutations were detected in 80 out of 98 mutant alleles (82%), including 19 missense (63%), 5 nonsense (17%), 3 splice-site (10%) and 3 deletions (10%). Most mutations were detected in exons 3, 6, 7, 11 and intron 4 of PAH gene. The most frequent mutations were p.R243Q (19%), IVS4-1G>A (9%), p.Y356X (7%) and p.EX6-96A>G(5%). Two novel mutations p.N93fsX5 (c.279-282delCATC) and p.G171E (c.512G>A) were found. p.H64fsX9(c.190delC) was documented for the second time in Chinese PAH gene. The mutation spectrum of the gene PAH in the Qinghai population was similar to that in other populations in North China while significantly different from that in the populations from some provinces in southern China, Japan and Europe. Conclusions The mutations of PAH gene in the Qinghai area of China demonstrate a unique diversity, complexity and specificity.

Key words

Phenylketonuria / Phenylalanine hydroxylase / Mutation

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HE Jiang, WANG Hui-Zhen, XU Fa-Liang, YANG Xi, WANG Rui, ZOU Hong-Yun, YU Wu-Zhong. Mutation analysis of the PAH gene in children with phenylketonuria from the Qinghai area of China[J]. Chinese Journal of Contemporary Pediatrics. 2015, 17(11): 1221-1227 https://doi.org/10.7499/j.issn.1008-8830.2015.11.014

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