青海地区汉族苯丙酮尿症患者苯丙氨酸羟化酶基因突变分析

摘要
图/表
参考文献
相关文章 (8)

全文: PDF (598 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要目的明确青海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,为该地区PKU的产前诊断和遗传咨询提供理论依据。方法应用PCR产物直接测序法对32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 (1)在64个PAH等位基因中检测出22种不同的突变等位基因共55个,总检测率为85.9%,其中,错义突变13种(59.1%)、无义突变5种(22.7%)、缺失突变3种(13.6%)、剪切位点突变1种(4.5%),大部分突变集中在第3、6、7、5、11外显子及两侧内含子区域,最常见的4种突变是p.R243Q(23.4%)、IVS4-1 G>A(10.9%)、p.Y356X(9.4%)、p.EX6-96A>G(7.8%),较常见的突变为p.N93fsX5(3.1%)、p.R111X(3.1%)、p.R400K(3.1%)和 p.Q232X(3.1%)。(2)p.R243Q是青海地区汉族PAH基因最常见的突变种类, 青海地区检出的p.N93fsX5和p.G171E是国际上汉族人群中首次报道的新的PAH基因突变,p.H64fsX9突变为国内第二次报道。结论青海地区汉族PAH基因的突变构成与国内北方某些地区相似,但部分突变基因比例存在明显差异,p.R243Q、IVS4-1G>A、p.Y356X和p.EX6-96A>G可能属于青海汉族人群中PAH基因突变的热点,p.N93fsX5、p.G171E和p.H64fsX9可能是青海汉族特有的PAH基因突变类型。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	何江
	徐发亮
	王惠珍
	杨曦
	王瑞
	邹红云
	余伍忠

关键词 ：苯丙酮尿症, 苯丙氨酸羟化酶, 突变

Abstract：Objective To describe mutation characteristics of the phenylalanine hydroxylase (PAH) gene in phenylketonuria (PKU) patients in Han ethnic group in Qinghai Province, in order to provide basic information for genetic counseling and prenatal diagnosis of PKU. Methods Mutations of the PAH were detected in promoter and exons 1-13 with flanking introns by PCR and DNA sequencing in 32 Han families with PKU. Results A total of 22 different mutations were detected in 55 out of 64 mutant alleles (85.9%), including 13 missense (59.1%), 5 nonsense (22.7%), 3 deletion (13.6%) and 1 splicing site (4.5%). Most mutations were detected in exons 3, 6, 7, 5, 11 and flaking introns. The most frequent mutations were p.R243Q (23.4%), IVS4-1G>A (10.9%), p.Y356X (9.4%) and p.EX6-96A>G (7.8%), followed by p.N93fsX5 (3.1%), p.R111X (3.1%), p.R400K (3.1%) and p.Q232X (3.1%). p.R243Q was the most prevalent mutation. Two novel mutations, p.N93fsX5 and p.G171E, were firstly identified in Han ethnic group and the p.H64fsX9 was the second documented in Chinese. Conclusion The mutation spectrum of PAH in Han ethnic group in Qinghai was similar to some Northern populations of China with obvious difference in mutation rate for some mutations. It suggests that p.R243Q, IVS4-1G>A, p.Y356X and p.EX6-96A>G are the hot spots of PAH mutations in Han ethnic group of Qinghai. p.N93fsX5, p.G171E and p.H64fsX9 are probably specific mutations of Han ethnic group in Qinghai Province, China.

Key words： Phenylketonuria Phenylalanine hydroxylase Mutation

收稿日期: 2015-02-11

通讯作者: 余伍忠(yuwz2013@126.com) *为同等贡献

引用本文:

何江, 徐发亮, 王惠珍, 杨曦, 王瑞, 邹红云, 余伍忠. 青海地区汉族苯丙酮尿症患者苯丙氨酸羟化酶基因突变分析[J]. 中国生育健康杂志, 2015, 26(6): 512-517.
HE Jiang, XU Faliang, WANG Huizhen, YANG Xi, WANG Rui, ZOU Hongyun, YU Wuzhong. Mutation analysis of the phenylalanine hydroxylase gene in patients with phenylketonuria in Han ethnic group of Qinghai Province, China. Chinese Journal of Reproductive Health, 2015, 26(6): 512-517.

链接本文:

http://cjrh.bjmu.edu.cn/CN/ 或 http://cjrh.bjmu.edu.cn/CN/Y2015/V26/I6/512

1 Woo SL,Lidsky AS,Guttler F,et al.Clone human phenylalanine hydroxylase gene allows prenatal diagnosis and carroer detection of classical phylketonuria.Nature,1983,306:151-155.
2 Song F,Qu YJ,Zhang T,et al.Phenylketonuria mutation in northern China.Mol Genet Metab,2005,86:S107-S118.
3 Hamzehloei T,Hosseini SA,Vakili R,et al.Mutation spectrum of the PAH gene in the PKU patients from Khorasan Razavi province of Iran.Gene,2012,506:230-232.
4 Daniele A,Scala I,Cardillo G,et al.Functional and structural characterization of novel mutations and genotype-phenotype correlation in 51 phenylalanine hydroxylase deficient families from southern Italy.Febs J,2009,276:2048-2059
5 Couce ML,Boveda MD,Femandez-Marmiesse A,et al.Molecular epidemiology and BH4-responsiveness in patients with phenylalanine hydroxylase deficiency from Galicia region of Spain.Gene,2013,521:100-104.
6 Guldberg P,Romano V,Cerattp NP,et al.Mutational spectrum of phenylalanine hydroxylase defiency in Sicily:implications for diagnosis of hyper pheenylalaninemaia in Southern Europe.Hum Mol Genet,1993,2:1703-1707.
7 高伟华,张全斌,刘建平,等.山西省经典型苯丙酮尿症患者苯丙氨酸羟化酶基因突变研究.中华医学遗传学杂志,2011,28:393-396.
8 毛新梅,何江,刘媛,等.宁夏汉族苯丙氨酸羟化酶基因突变分析.中国儿童保健杂志,2013,21:351-354.
9 郭红军,赵振华,江森,等.河南地区苯丙酮尿症患者苯丙氨酸羟化酶基因突变研究.中华医学遗传学杂志,2011,28:142-146.
10 卢超霞,高峡,王金玮,等.河北地区55例苯丙酮尿症患者苯丙氨酸羟化酶基因突变的检测与分析.中华医学杂志,2011,91:2971-2976.
11 Zhu TW,Qin SY,Ye J,et al.Mutational spectrum of phenylketonuria in the Chinese Han population:a novel insight into the geographic distribution of the common mutations.Pediatr Res,2010,67:280-285.
12 Yu WZ,Qiu DH,Song F,et al.Mutation characteristics of the PAH gene in four Nationality groups in Xinjiang of China.J Genet,2008,87:293-297.
13 Shen DY,Wu W,Zhao ZY.Mutations in patients with hyperphenylalaninemia in zhejiang,China.Genes & Genomics,2009,31:85-88.
14 Johamnes Z.Phenylketonuria mutations in Europe.Hum Mutat,2003,21:345-356.
15 宋力,党利亨,孟英韬,等.天津及周边地区苯丙氨酸羟化酶基因突变谱和新突变分析.中华医学遗传学杂志,2010,27:7-12.
16 瞿宇晋,宋昉,金煜炜,等.北京地区苯丙酮尿症基因突变构成及基因型与表型相关分析.中华儿科杂志,2008,46:115-119.
17 张军力,孟峻,翟晓萍,等.经典型苯丙酮尿症苯丙氨酸羟化酶基因的新突变鉴定.中华医学遗传学杂志,2005,22:134-137.
18 邵诸君,王凤羽,耿尧,等.苯丙氨酸羟化酶基因突变及其与表型的关系研究进展.中国优生与遗传杂志,2010,18:1-3.
19 宋昉,瞿宇晋,杨艳玲,等.中国北方地区苯丙氨酸羟化酶基因的突变构成.中华医学遗传学杂志,2007,24:241-246.
20 Okano Y,Asada M,Kang Y,et al.Molecular characterization of phenylketonuria in Japanese patients.Hum Genet,1998,103:613-618.
21 张菁菁,孙云,孙亦骏,等.江苏地区高苯丙氨酸血症患儿苯丙氨酸羟化酶基因突变谱和新突变研究.中华医学遗传学杂志,2013,30:513-517.
22 Kobe B,Jennings IG,House CM,et al.Structural basis of autoregutation of phenylalanine hydroxylase.Nat Struct Biol,1999,6:442-448.
23 Erlandsen H,Patch MG,Gamez A,et al.Structural studies on phenylalanine hydroxylase and implications toward understandingand treating phenyiketonuria.Pediatrics,2003,112:1557-1565.