摘要
目的：检测苯丙酮尿症（PKU）患儿及其父母苯丙氨酸羟化酶（PAH）基因突变谱，并探讨 PAH 基因突变与临床严重程度的相关性，为本地区 PKU 患儿的早期诊断及遗传咨询提供基础数据。方法使用高通量测序技术对来自江苏省无锡和宿迁的32例 PKU 患儿及其父母的 PAH 基因13个外显子及其附近内含子区域进行测序分析。结果32例 PKU 共检测出61个突变位点，33种突变基因，突变检出率为95.31％（61/64个）。本地区 PKU 患儿常见致病突变位点为 c.721C ﹥ T、c.1068C ﹥ A、c.611A ﹥ G、c.1197A ﹥ T、c.728G ﹥ A、c.331C ﹥ T 和 c.442-1G ﹥ A，其突变频率均在5％以上。首次报道1个新的突变基因位点 c.699C ﹥ G 和3个汉族人口中新的突变基因位点 c.265C ﹥ T、c.722G ﹥ A 和 c.1194A ﹥ G。Guldberg AV 系统分析显示38.0％（8/21例）的 PKU 患者基因型与实际生化表型相一致，其中预测表型为中重度的与实际生化表型的一致率为92.3％（12/13例），轻度的与实际生化表型的一致率为50.0％（4/8例）。结论江苏地区 PKU 患儿的 PAH 基因突变集中在外显子7上，其中频率最高的基因位点是 c.721C ﹥ T，并首次发现1个新的基因突变位点 c.699C ﹥ G；PKU 患者基因型与生化表型之间有一定的相关性。
Objective By detecting the mutations spectrum of phenylalanine hydroxylase（PAH）gene in phe-nylketonuria（PKU）patients and their parents. The researchers analyzed the gene mutation features and high - frequency mutations and determined the relationship between the genotype and the phenotype,which would provide a theoretical basis for the early diagnosis and genetic consultation of PKU children in the region. Methods In this study,13 exons and their flanking introns of the PAH gene in 32 PKU patients and their parents from Wuxi and Suqian in Jiangsu province were sequenced by using the next - generation sequencing（NGS）technology. Results Sixty - one mutant sites and 32 mutant genes were detected in 32 PKU patients,and the mutation detection rate was 95. 31%（61 / 64 cases）. The variants at c. 721C ﹥ T,c. 1068C ﹥ A,c. 611A ﹥ G,c. 1197A ﹥ T,c. 728G ﹥ A,c. 331C ﹥ T and c. 442 -1G ﹥ A were common mutations in the region with mutation frequency over 5% . What＆#39;s more,4 novel variants of c. 699C ﹥ G,c. 265C ﹥ T,c. 722G ﹥ A and c. 1194A ﹥ G were found. Of those,c. 699C ﹥ G was not recorded in the PAH variant database and HGMD database and. c. 265C ﹥ T,c. 722G ﹥ A,and c. 1194A ﹥ G were first reported in the Chi-nese population. Genotype - accurate biochemical phenotype correlation by using the Guldberg AV system revealed con-sistency rate of 38. 0%（8 / 21 cases）,which the consistency rate between accurate biochemical phenotype and predic-tive phenotype of moderate to severe genotype was 92. 3%（12 / 13 cases）,and mild genotype was 50. 0%（4 / 8 cases）. Conclusions The PAH gene variants of PKU patients in Jiangsu province are distributed mainly in exons 7,of which the highest frequency gene mutation is c. 721 c ﹥ T. Moreover,one novel variant c. 699C ﹥ G was reported for the first time. The PKU children inherit the PAH mutation gene mainly from both parents. There are definite correlation between the genotypes and phenotypes.
出处
《中华实用儿科临床杂志》
CAS
CSCD
北大核心
2015年第20期1554-1556,共3页
Chinese Journal of Applied Clinical Pediatrics
基金
江苏省卫生厅科研项目（H201245）
