新疆地区苯丙氨酸羟化酶基因的突变研究

Characteristics of the PAH gene mutation in Chinese patients with phenylketonuria in Xinjiang

目的了解新疆地区苯丙氨酸羟化酶（phenylalanine hydroxylase，PAH）基因的突变规律及特点。方法应用聚合酶链反应-单链构象多态性分析及基因测序列方法，检测46例苯丙酮尿症患者PAH基因第3、5、6、7、11和12外显子及其两侧内含子序列。结果在92个PAH等位基因中共检出20种不同的突变基因，总检出率为73．9％（68／92）。其中常见基因突变R243Q、EX6—96A〉G、R111X、Y356X和V399V与我国北方地区基本类似。较常见基因突变F161S、L255S、P281L和R413P与国内其他地区相比差异较大。E280G和A434D为在国际上第2次检出；L255S、P281L、R261Q和165T为在国内第2次检出。新疆少数民族也发现了13种PAH基因突变，均系在本民族中首次报道，其突变基因的类型表现出鲜明的民族特色。结论从对新疆地区PAH突变基因的研究结果来看，该地的遗传基因不仅具有独立、保守的特性，而且还存在着相互交叉、相互融合的特征。

Objective To study the characteristics of the PAH gene mutation in patients with phenylketonuria （PKU） in Xinjiang area. Methods The mutations in exons 3, 5, 6, 7, 11 and 12 and the flanking intronic sequence of the PAH gene were detected by PCR/SSCP analysis and direct DNA sequencing in 46 PKU patients. Results Twenty different mutations were found in 68/92 alleles （73. 9%）. The prevalent mutations of R243Q, EX6-96A〉G, R111X, Y356X and V399V were similar to that of Northern China populations. The mutations F161S, L255S, P281L, and R413P were significantly different from that in other Chinese populations. It was the second time that E280G and A434D mutations were reported in the world, that L255S, P281L, R261Q, and I65T mutations were found in China. Thirteen different mutations were first found in Chinese Uygur, which showed a distinct ethnic characteristics. Conclusion The study showed not only a distinct and conservative, but also a crossed and syncretic genetic characteristics in Xinjiang Uygur population. The results suggest that Xinjiang could be an ideal genetic resource repertoire for studying diversity of gene mutations, heterogeneity of PAH gene, human origins and migration.