摘要
目的探讨徐州地区新生儿苯丙酮尿症(phenylketonuria,PKU)筛查特征及构建徐州地区苯丙氨酸羟化酶(phenylalanine hydroxylase,PAH)基因和四氢生物蝶呤缺乏症相关基因突变谱。方法选择2015年11月至2020年3月徐州地区出生并采用串联质谱技术进行苯丙氨酸(Phe)及苯丙氨酸与酪氨酸比值(Phe/Tyr)测定的新生儿资料进行回顾性研究,应用高通量测序联合Sanger测序技术对苯丙氨酸异常患儿进行基因分析。结果共计完成450355名新生儿苯丙氨酸相关指标测定,确诊115例PKU,患儿Phe及Phe/Tyr比值显著升高,PKU发病率为1∶3916。其中PAH基因突变113例,PTS基因突变2例。PAH基因突变患儿中纯合子突变5例,PAH合并PTS双基因突变1例,PAH基因3位点突变2例。PAH基因高频突变类型为2号外显子错义突变,常见基因突变主要包括c.158G>A(p.R53H)(24.7%,56/227)、c.728G>A(p.R243Q)(15.0%,34/227)、c.611A>G(p.Y204C)(5.3%,12/227)、c.721C>T(p.R241C)(5.3%,12/227)和c.1068C>A(p.Y356X)(4.8%,11/227)。共发现3个新的PAH基因突变(c.234dupA、c.441+15C>G和c.1096C>T)及1个新的PTS基因突变(c.286G>A)。结论徐州地区PKU较常见,属于PKU高发地区,基因突变以PAH基因突变为主。
Objective To study the characteristics of phenylketonuria(PKU)using tandem mass spectrometry for neonatal screening and the characteristics of genetic mutation spectrums of phenylalanine hydroxylase(PAH)deficiency and pyruvoyl-tetrahydropterin synthase(PTS)deficiency in Xuzhou area.Method From November 2015 to March 2020,the phenylalanine(Phe)level and the ratio of phenylalanine to tyrosine(Phe/Tyr)were examined using tandem mass spectrometry.The infants with abnormal Phe level and Phe/Tyr ratio were further analyzed using high-throughput sequencing combined with Sanger sequencing.Result 450355 neonates were enrolled.Phe levels and Phe/Tyr ratios were increased in 115 neonates.The incidence of PKU was 1∶3916.113 cases showed PAH gene mutation and 2 cases PTS gene mutation.Common genetic variations of PAH gene included c.158G>A(p.R53H)(24.7%,56/227),c.728G>A(p.R243Q)(15.0%,34/227),c.611A>G(p.Y204C)(5.3%,12/227),c.721C>T(p.R241C)(5.3%,12/227)and c.1068C>A(p.Y356X)(4.8%,11/227).R53H was located on Exon2.In addition,3 novel variants of PAH gene including c.234dupA,c.441+15C>G and c.1096C>T and 1 novel variant of PTS gene c.286G>A were identified.Conclusion PKU is relatively common in Xuzhou area with a high incidence.The variants were mainly located on PAH gene.
作者
周伟
李惠中
杨丽
王传霞
董步连
黄腾
顾茂胜
Zhou Wei;Li Huizhong;Yang Li;Wang Chuanxia;Dong Bulian;Huang Teng;Gu Maosheng(Xuzhou Maternity and Child Health Care Hospital,Xuzhou Branch of Jiangsu Neonatal Disease Screening Center,Xuzhou 221000,China)
基金
江苏省研究生科研与实践创新计划项目(KYCX19_2211)
徐州市科技计划项目(KC19028)。
作者简介
通信作者:顾茂胜,Email:gumaoshcng2007@126.com。
