山东省30例苯丙酮尿症患者苯丙氨酸羟化酶基因的突变分析

Mutation Analysis of Phenylalanine Hydroxylase Gene in 30 Patients with Phenylketonuria in Shandong Province

目的研究山东省30例苯丙酮尿症患儿苯丙氨酸羟化酶基因的突变特点。方法使用二代测序技术结合生物信息学分析手段检测PAH缺乏型苯丙酮尿症患者PAH基因的变异位点。结果30例患者的60个PAH等位基因中共检测出53个PAH基因位点突变,检出率为88.3%。检测出的27种PAH基因的突变类型包括17种错义突变、4种无义突变、4种剪接突变、1种同义突变和1种移码突变。突变分布在第1-3、5-7、10-12号外显子和第4号、5号、7号、12号内含子上。其中热点突变为c.728G>A(24.53%)、c.721C>T(7.55%)和c.1238G>C(5.66%),新突变位点为:c.155T>G和c.621T>A。结论山东省30例PKU患儿的PAH基因突变以错义突变为主,主要发生在第7号外显子上。研究检测出PAH基因的27个突变位点,包括2个新的突变位点,为苯丙酮尿症的产前诊断和机制研究提供依据。

Objectives To study the mutation characteristics of phenylalanine hydroxylase(PAH)gene in 30 children with Phenylketonuria in Shandong province.Methods The second-generation sequencing technology combined with bioinformatics analysis was used to detect the mutation sites of PAH gene in patients with PAH deficiency phenylketonuria.Results A total of 53 PAH gene site mutations were detected in 60 PAH alleles of 30 patients,with a detection rate of 88.3%.The 27 PAH gene mutations detected include 17 missense mutations,4 nonsense mutations,4 splicing mutations,1 synonymous mutation and 1 frameshift mutation.The mutations were distributed in exons 1-3,5-7,10-12 and introns 4,5,7 and 12.The hot spots were C.728G>A(24.53%),C.721C>T(7.55%)and C.1238G>C(5.66%),and the new mutations were c.155T>G and C.621T>A.Conclusions The mutation of PAH gene in 30 children with PKU in Shandong province is mainly missense mutations,which mainly occurs in exon 7.In this study,27 mutation sites of PAH gene were detected,including 2 new mutation sites,which provided a basis for prenatal diagnosis and mechanism research of phenylketonuria.