福建地区36例苯丙氨酸羟化酶缺乏症患儿的基因突变分析

Genetic analysis of 36 children affected with phenylalanine hydroxylase deficiency from Fujian

目的分析福建地区苯丙氨酸羟化酶（phenylalanine hydroxylase，PAH）缺乏症患儿及父母的PAH基因突变特征。为患儿的基因诊断及父母和患儿本人提供遗传咨询和生育指导奠定基础。方法收集36例患儿及父母的外周静脉血，应用PCR测序技术检测其PAH基因并分析该基因的突变情况。结果在72个PAH等位基因中，63个PAH等位基因含20种致病性突变，包含3种无义突变，12种错义突变，3种剪接突变，1种同义突变和1种移码终止突变。高频突变位点主要是R241C、R408Q和EX6-96A〉G，分别占15．9％、12．7％和11．1％。其中c．189-190dupTGAC尚未见报道。28％的轻度高苯丙氨酸血症（mild hyperphenylalaninemia，MHP）基因突变型为R241C，25％的经典型苯丙酮尿症（phenylketonufia，PKU）基因突变型R408Q。结论福建地区苯丙氲酸羟化酶缺乏症患儿PAH基因突变型有别于中国的其他区域，主要是R241C、R408Q和EX6-96A〉G。其中R241C和R408Q主要分则与MHP和经典型PKU有关。

Objective To study the characteristics of phenylalanine hydroxylase gene （PAH） mutations in patients with PAH deficiency in Fujian population. Methods Peripheral blood samples of 36 patients and their parents with classical type phenylketouria （PKU） were collected. Genomic DNA was extracted. Following PCR amplification, DNA sequencing was carried out to identify the origins of mutations. Results Twenty types mutations were identified in 63 of the 72 alleles. The most common mutations were R241C, R408Q and Ex6-96A〉G, which respectively accounted for 15.9%, 12.7 % and 11.1 % of all mutant alleles. The c. 189-190dupTGAC mutation was first reported. R241C was associated with 28 % of mild hyperphenylalaninemia and R408Q is associated with 25 % of classical PKU. Conclusion There is a specific spectrum of PAH gene mutation in Fujian region. R241C, R408Q and Ex6-96A〉G are the most common mutations.