中国西北地区汉族苯丙酮尿症患者苯丙氨酸羟化酶基因突变分析  

Analysis on mutations of phenylalanine hydroxylase gene in Han ethnic patients with phenylketonuria from the Northwest region of China

作　　者：何江[1] 强荣 毛新梅 王慧珍 闫有圣[5] 邹红云[1] 史清海[1] HE Jiang;QIANG Rong;MAO Xin-Mei(Department of Laboratory Medicine,General Hospital of Xinjiang Military Region,PLA,Urumqi 830000,China)

机构地区：[1]新疆军区总医院检验科,新疆乌鲁木齐830000 [2]陕西省妇幼保健院医学遗传中心,陕西西安710003 [3]宁夏回族自治区妇幼保健院新生儿疾病筛查中心,宁夏银川750011 [4]青海省妇幼保健院新生儿疾病筛查中心,青海西宁810000 [5]甘肃省妇幼保健院医学遗传中心,甘肃兰州730050

出　　处：《中国实验诊断学》2022年第3期317-322,共6页Chinese Journal of Laboratory Diagnosis

基　　金：国家自然科学基金面上项目(81871020);新疆维吾尔自治区自然科学基金面上项目(2016D01C393)。

摘　　要：目的 分析中国西北地区汉族苯丙酮尿症(PKU)患者苯丙氨酸羟化酶(PAH)基因的突变特征。方法 应用PCR产物直接测序法对2003年1月-2019年8月在中国西北五省区新生儿疾病筛查中心或医学遗传中心确诊的223例汉族PKU患儿及其父母的PAH基因启动子、第1-13外显子及其旁侧内含子区域进行基因突变分析。结果在西北地区223例汉族PKU患者446条PAH等位基因中检测出75种致病突变,总检出率为88.6%(395/446),突变以错义突变(66.7%)、剪切位点突变(16.0%)和无义突变(9.3%)为主;大部分突变主要分布在外显子7(29.0%)、外显子6(10.5%)、外显子3(10.3%)、外显子11(9.6%)、外显子12(8.5%)和第4内含子(6.7%)中;突变频率较高的PAH基因致病突变是R243Q(22.1%)、IVS4-1G>A(6.7%)、EX6-96A>G(6.5%)、R111X(5.4%)、R53H(4.3%)、Y356X(4.0%)、R413P(3.8%)和V399V(3.1%);西北汉族最常见PAH基因突变(R243Q)与中国北方基本一致,但显著区别于日本(R413P)、巴西(V388M)、德国(R408W)、立陶宛(R408W)和美国(R408W)等国家。研究发现7种国际上未见报道的新突变:N93fsX5、G171E、P225S、Q304K、H107R、F392I和N223I。结论 西北汉族PKU患者PAH基因致病突变构成与中国北方类似,但显著区别于部分亚洲和欧美国家,西北汉族的PAH基因突变谱具有其独特保守的地域特征,推测R243Q突变的高发在中国北方地区,而R408W突变的高发在欧洲地区。Objective To investigate the mutation characteristics of the phenylalanine hydroxylase(PAH)gene in Han ethnic patients with phenylketonuria(PKU)from the Northwest region of China.Methods PCR product direct sequecing were used in combination with the gene mutation analysis in PAH gene promoter,1-13exons and adjacent introns in 223Han ethnic children and their parents of families with PKU which were diagnosed in the neonatal disease screening centers or medical genetic centers of five provinces in northwest China from January 2003to August 2019.Results Three hundred and ninety-five pathogenic mutation alleles were found in 223Han ethnic patients with PKU and accounting for 88.6%(395/446).A total of 75different mutations were detected,mainly including missense mutation(66.7%),splicing mutation(16.0%)and nonsense mutation(9.3%).Most mutations existed in exon 7(29.0%),exon6(10.5%),exon 3(10.3%),exon 11(9.6%),exon 12(8.5%)and intron 4(6.7%).The most common mutations were R243Q(22.1%),IVS4-1G>A(6.7%),EX6-96A>G(6.5%),R111X(5.4%),R53H(4.3%),Y356X(4.0%),R413P(3.8%)and V399V(3.1%).Similar to most provinces of Northern China,R243Qwas the most common mutation type in Han ethnic patients with PKU from the Northwest region of China and this was different from Japan(R413P),Brazil(V388M)and some European and American countries(R408W)such as Germany,Lithuania,The United States,etc.N93fsX5,G171E,P225S,Q304K,H107R,F392Iand N223Iwere ascertained to be seven kinds of novel PAHgene mutations worldwide.Conclusion The mutation soectrum of PAHgene in Han ethnic patients with PKU from the Northwest region is simimar to the Northwest region of China,but different from that of some countries in Asia and Europe and America,which diaplays a distinct and conservative characteristic.It is speculated that the mutation height of R243Qis in northern China,while the mutation height of R408Wis in Europe.

关 键 词：苯丙酮尿症 苯丙氨酸羟化酶 突变 汉族 

分 类 号：R596.1[医药卫生—内科学]