Abstract: Objective To investigate the characteristics of gene mutations in children with hyperphenylalaninemia(HPA) in some regions of Sichuan, so as to provide basis for genetic diagnosis, prenatal diagnosis and genetic counseling of patients. Method PAH, PTS, QDPR, PCBD1, SPR and GCH1 genes of 43 HPA children were analyzed by next-generation sequencing technology (NGS). Results Totally 35 cases with PAH gene mutation and 8 cases with PTS gene mutation were detected.The most common mutations of PAH in the top three were p.R243Q, p.R241C and p.Ex6-96A>G.Finally 28 mutations (39.4%) were identified in exon 7.The p.G272V mutation of PAH had not been reported previously.The p.P87S, p.Y27Rfs*8, p.D96N and p.V56M mutations were the most common mutations of PTS.And 8 mutations (50.0%) were identified in exon 5.The p.T58R mutation of PTS was not reported previously. Conclusion The mutational spectrum of HPA-related genes in some regions of Sichuan is preliminarily constructed in this study, and a new mutation is detected in PAH and PTS respectively, which will provide reliable basis for genetic diagnosis and genetic counseling of patients with HPA in this region.

Key words: hyperphenylalaninemia, phenylalanine hydroxylase, 6-pyruvoyl tetrahydropterin synthase, gene mutation

摘要： 目的 了解四川省部分地区高苯丙氨酸血症(HPA)患儿基因突变情况,构建本地区HPA相关基因突变谱,为患儿基因诊断、产前诊断及遗传咨询提供依据。方法 采用第二代测序技术对43例HPA患儿的PAH、PTS、QDPR、PCBD1、SPR及GCH1基因进行分析。结果 检出PAH基因突变35例,PTS基因突变8例。占前3位的PAH高频突变为p.R243Q、p.R241C及p.Ex6-96A>G,高频突变的区域为第7外显子,包含了28个突变(39.4%)。p.G272V未见报道。PTS基因的高频突变位点为p.P87S、p.Y27Rfs*8、p.D96N及p.V56M,高频突变区域为第5外显子,包含了8个突变(50.0%)。p.T58R未见报道。结论 本研究初步构建了四川省部分地区HPA相关基因的突变谱,在PAH和PTS基因上各发现1个新突变,为本地区HPA患儿的基因诊断和遗传咨询提供了依据。

关键词: 高苯丙氨酸血症, 苯丙氨酸羟化酶, 6-丙酮酰四氢蝶呤合成酶, 突变