Abstract：Objective To investigate the mutation characteristics of the phenylalanine hydroxylase(PAH)gene in Northewest Chinese patients with phenylketonuria(PKU)and to provide a theoretical basis for genetic diagnosis and consultation of PKU at the prenatal stage.Methods Through combining the methods of PCR direct sequencing, gene chip and high throughput sequencing, we detected the mutations in PAH gene promoter, 1-13 exons and adjacent introns among 326 children and their patients, who were recruited from the patients diagnosed by the neonatal disease screening Centers in the five northwestern provinces of China from January 2003 to December 2019.Results Among 326 PKU patients, out of 652 alleles, 105 different mutations were detected. The total detection rates were 87.7%. The major types of mutations are missense mutation, splicing mutation, nonsense mutation and frameshift mutations. Most mutations are located in exon 79 (25.2%), followed by exon 6 (11.8%), exon 3 (9.2%), exon 12 (9.2%), exon 11 (8.3%), intron 4 (5.2%), exon 2 (3.5%) and exon 2 (3.5%). The most common mutation was R243Q, which is the same to the most common mutation in Northern China and Korea, but different from that in Japan (R413P), Germany (R408W), Israel (IVS10-11G>A), Italy (R261Q), Brazil (V388M) and the United States (R408W). The other common mutations included EX6-96A>G, IVS4-1G>A, R413P, R111X, Y356X, R53H, R241C and IVS7+2T>A. The frequencies of R243Q, R413P and EX6-96 A>G mutations of ethnic Han group were significantly different from those of Uygur group. In Northwest China, the frequency of R243Q mutation was significantly higher than that in Japan or Korea (P<0.05). Fourteen new PAH gene mutations were reported for the first time. Additional nine mutations were first identified among the Chinese population.Conclusion Among Northwestern Chinese, mutation spectrum of PAH gene is similar to that in Northern China, but slightly different from that in Japan, Korea and other East Asian countries, or significantly different from that in West Asian, European and American countries. The PAH gene profiles in Northwest China are independent and conservative. The R243Q mutation is probably originated from Han ethnicity; R241C and Q232X are from Hui ethnicity; and R413P, F161S, IVS10-11G>A, P281L and IVS11-2A>C are from Uygur ethnicity.
何江, 强荣, 毛新梅, 徐发亮, 闫有圣, 余伍忠, 史清海. 中国西北地区苯丙氨酸羟化酶基因突变构成分析[J]. 中国生育健康杂志, 2021, 32(6): 531-539.
HE Jiang, QIANG Rong, MAO Xinmei,XU Faliang, YAN Yousheng, YU Wuzhong, SHI Qinghai. Analysis on mutation spectrum of phenylalanine hydroxylase gene in Northwest Chinese patients with phenylketonuria. Chinese Journal of Reproductive Health, 2021, 32(6): 531-539.
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