新疆地区苯丙氨酸羟化酶基因外显子7的突变研究  

Mutations in exon 7 of the PAH gene in Chinese phenylketonuria patients in Xinjiang

作　　者：余伍忠[1] 仇东辉[1] 宋昉[2] 刘丽[1] 金煜炜[2] 何江[1] 桂俊豪[1] 王瑞[1] 邹红云[1] 王铮[1] 周郁[1] 雷权[1] 张占平[3] 刘兴文[4] 

机构地区：[1]兰州军区乌鲁木齐总医院临床医学研究所,乌鲁木齐830000 [2]首都儿科研究所 [3]解放军第十二医院检验科 [4]解放军第十二医院妇产科

出　　处：《中华检验医学杂志》2007年第6期641-644,共4页Chinese Journal of Laboratory Medicine

摘　　要：目的研究分析新疆地区苯丙酮尿症(PKU)患者中苯丙氨酸羟化酶(PAH)基因外显子7的突变特征。方法用 PCR 及单链构象多态性(SSCP)分析技术结合基因序列测定法,对37例PKU 患者进行 PAH 基因外显子7突变筛查和鉴定。结果从37例 PKU 患者(共74条染色体)中,发现20条染色体等位基因异常,经测序鉴定共检出5种错义突变,即 R243Q、L255S、E280G、E280K和 P281L,等位基因突变检出率为27%。其中 R243Q 频率最高(18.9%),L255S 次之(4.1%),而E280G、E280K 和 P281L 仅为1.4%。在5种基因突变中,E280G 为在国际上第2次发现,L255S、E280K 和 P281L 为在国内第2次检出。维吾尔族群体也检出了2例突变,分别是 P281L 和 R243Q,均为在本地区维吾尔族中首次报道。查阅国内外研究结果结合本结果分析后发现,R243Q 是亚洲黄种人常见的突变体,P281L 和 E280K 是欧洲及拉美等国较为普遍存在的突变型,而 E280G 与 L255S 则是具有中国特色的基因突变。结论新疆 PKU 基因突变类型及频率具有明显的地区特点,是我国与欧亚地区之间相互区别、又相互联系的一个较为特殊的 PAH 突变基因分布带,也是研究基因突变多样性、PAH 基因异质性特点以及人类起源、迁徙等的理想资源地。Objective To investigate the mutation characteristics in exon 7 of the PAH gene in phenylketonuria（PKU） patients in Xinjiang. Methods The mutations in exon 7 of PAH gene were detected by PCPJSSCP in 37 PKU patients. Results Five missense mutations including R243Q, L255S, E280G, E280K and P281L were identified in 74 chromosomes from 37 PKU patients, with relative frequencies of 18. 9%, 4. 1%, 1.4%, 1.4% and 1.4% respectively. The frequency of mutant alleles in exon 7 was 27%. Among the five mutations, it was the second time the E280G mutation was reported in the world. In China,it was the second time the L255S, E280K and P281L mutations were found. P281L and R243Q mutations were first found in 2 of Chinese Uygur. Considering the previous reports and the present study, R243Q was the most prevalent form in Asian PKU populations. P281L and E280K were two common mutations in PKU patients from European countries. However, E280G and L255S were two characteristic forms in Chinese. Conclusions Characteristics of PAH gene mutations are shown in Chinese PKU population from Xinjiang, which is a special distribution belt that located between China and Europe. The results give a clue that Xinjiang could probably be an ideal genetic resource repertoire for studying diversity of gene mutations, heterogeneity of PAH gene, human genesis and migration.

关 键 词：苯丙酮尿症 苯丙氨酸羟化酶 基因突变 外显子 

分 类 号：R450[医药卫生—治疗学]