连云港地区苯丙酮尿症患儿苯丙氨酸羟化酶基因突变谱的构建及其应用  

Construction and application of phenylalanine hydroxylase gene mutational spectrum of the child patients with phenylketonuria in Lianyungang area

作　　者：王震文[1] 周保成[1] 毛华芬[1] 刘双[1] 尹婷[1] 顾莹[1] 

机构地区：[1]连云港市妇幼保健院产前诊断中心,江苏连云港222006

出　　处：《临床检验杂志》2016年第5期362-365,共4页Chinese Journal of Clinical Laboratory Science

基　　金：江苏省妇幼保健科研项目(F201236)

摘　　要：目的分析连云港地区苯丙酮尿症（PKU）患儿苯丙氨酸羟化酶（PAH）基因突变特点,构建PAH基因突变谱,探讨PKU患儿基因型与表型的关系。方法用二代测序技术分析29例PKU患儿及其父母PAH基因第1～13外显子及两侧内含子序列,用AV值评分法进行基因型-生化表型的预测。结果 29例PKU患儿的58个等位基因中共检测出50个突变,检出率为86.2%,常见突变依次为R243Q（11/50,22.0%）,R241C（4/50,8.0%）和V399V（4/50,8.0%）;R169S和P292L为新发突变;通过基因型预测的生化表型与患儿实际生化表型的一致率为80.0%,其中经典型PKU的预测一致率为83.3%,患儿治疗前血苯丙氨酸水平与AV值评分呈显著负相关（r=-0.71,P〈0.05）。结论连云港地区PKU患儿PAH基因突变谱与其他地区有差别,基因型与表型之间具有相关性,对临床治疗具有重要指导意义。Objective To investigate the characteristics of phenylalanine hydroxylase（ PAH） gene mutations of the child patients with phenylketonuria（ PKU） in Lianyungang area,construct the mutational spectrum of PAH gene and analyze the relationship between the genetype and phenotype in the child patients with PKU. Methods Twenty-nine child patients with PKU and their parents were enrolled in this study. All of 13 exons and their flanking introns sequences of PAH gene in these subjects were directly sequenced by the Ion Torrent PGMTM sequencing technology. The genetype and biochemical phenotype were predicted with arbitrary value（ AV） scoring. Results A total of 50 mutations（ 50 /58,86. 2%） were detected from 58 allelic genes of 29 child patients. The prevalent mutations included R243Q（ 11 /50,22. 0%）,R241C（ 4 /50,8. 0%） and V399V（ 4 /50,8. 0%）. Two new mutations,such as R169 S and P292 L,were detected. The consistency of biochemical phenotypes between the predicted by genetypes and the actual observation was 80. 0%,and 83. 3% in classic PKU. The pretherapy phenylalanine levels in the child patients were negatively correlated with AV score（ r =- 0. 71,P〈0. 05）. Conclusion There is difference in the PAH gene mutational spectrum of PKU child patients between Lianyungang area and other regions,and there is correlation between the genetype and phenotype of PAH gene,which may play an important role in the treatment of PKU.

关 键 词：二代测序 苯丙酮尿症 苯丙氨酸羟化酶基因 基因型 

分 类 号：R725.8[医药卫生—儿科]