摘要
目的探讨江西地区苯丙酮尿症(phenylketonuria,PKU)患者苯丙氨酸羟化酶(phenylalanine hydroxylase,PAH)基因的变异特点,构建该地区PAH基因的变异谱,为该地区的PAH基因诊断及产前诊断提供依据.方法针对78个PKU家系应用PCR和Sanger测序对PAH基因的13个外显子及其侧翼序列进行分析,寻找致病变异位点.结果在78例患者的156个等位基因中,共检测到143个变异位点,共54种变异,检出率为91.7%.常见的变异依次为R243Q(26/143,18.2%)、R408Q(10/143,7.0%)、EX6-96A>G(8/143,5.6%)、IVS4-1G>A(7/143,4.9%)、R241C(7/143,4.9%),以及V399V(7/143,4.9%).IVS43T>G、Q172H、C284Y、V291L、V329del和L430R未见报道.变异的类型包括错义变异(31种)、剪接变异(12种)、无义变异(6种)和缺失变异(5种).变异主要集中在第7(45,31.5%)、12(17,11.9%)、11(16,11.2%)和6(14,9.8%)外显子.结论江西地区PAH基因变异频率最高者为R243Q,其次为R408Q,变异主要集中于第7、12、11、6外显子.此外,发现了6个新的基因变异.
Objective To delineate the variants spectrum of phenytalanine hydroxylase(PAH)gene among 78 unrelated patients with phenylketonuria(PKU)from Jiangxi province.Methods The 13 exons and flanking intronic regions of the PAH gene were subjected to PCR amplification and sequencing.Results A total of 143 variants were detected among the 156 alleles,which included 54 types of variants,which yielded a detection rate of 91.7%.Common variants have included R243Q(26/143,18.2%),R408Q(10/143,7.0%),EX6-96A>G(8/143,5.6%),IVS4-1G>A(7/143,4.9%),R241C(7/143,4.9%)and V399V(7/143,4.9%).In addition,6 novel variants were detected,which included IVS43T>G,Q172H,C284Y,V291L,V329del,and L430R.The variants consisted of missense,splicing,nonsense and deletion variants,which have mainly located in exons 7(45,31.5%),12(17,11.9%),11(16,11.2%)and 6(14,9.8%).Conclusion Variants of the PAH gene identified in Jiangxi province mainly involve exons 7,12,11 and 6,with the most common variants being R243Q and R408Q.Six novel variants were identified.
作者
陆清
刘艳秋
杨必成
谢康
邹永毅
卢婉
王枫
Lu Qing;Liu Yanqiu;Yang Bicheng;Xie Kang;Zou Yongyi;Lu Wan;Wang Feng(Jiangxi Maternal and Child Health Care Hospital,Nanchang,Jiangxi 330006,China)
出处
《中华医学遗传学杂志》
CAS
CSCD
2019年第11期1057-1061,共5页
Chinese Journal of Medical Genetics
基金
江西省重点研发计划项目(20161BBG70138)
国家自然科学基金(81741064).
作者简介
通信作者:王枫,Email:jxxs6519@163.com
