新疆少数民族苯丙酮尿症患者的突变基因分析

Identification of mutations in phenylalanine hydroxylase gene of Xinjiang minority nationality phenylketonuria patients

目的探讨新疆少数民族苯丙酮尿症（PKU）患者的基因突变特征，为有针对性的防治策略提供科学依据。方法采用单链构象多态性分析技术和PCR产物直接测序方法，检测12例少数民族PKU患者的苯丙氨酸羟化酶（PAH）基因突变。结果从12例维吾尔族、回族和哈萨克族PKU患者（24个PAH等位基因）中，检出13种基因突变，包括错义突变8种、无义突变1种、剪切位点突变3种，其中突变频率最高的是EX6—96A〉G和P281L，EX6—96A〉G常见于国内和亚洲地区，P281L多见于欧洲各地。突变频率较高的R243Q、R111X、R176X和F161S4种突变中，其中R243Q是我国北方地区居首位的突变，R111X处于第3位，而R176X和F161S在世界范围内都极为少见，尤其F161S是具有中国特色的基因突变，是第2次在中国人中发现。结论新疆少数民族中的PAH突变基因不仅与亚洲黄种人和欧洲及拉美人种表现出密切的联系，而且也存在着明显的差异，形成了自身独立的遗传规律和特点，是我国一个十分特殊的PAH突变基因分布区域。

Objective To study the mutation characteristics in phenylalanine hydroxylase gene of Xinjiang minority nationality phenylketonuria （PKU） patients and provide a scientific basis for PKU prevention and cure strategy. Methods Mutations in phenylalanine hydroxylase gene were detected by polymerase chain reaction-single strand comformation polymorphism（PCR/SSCP） and gene sequencing in 12 minority nationality patients. Results Thirteen different mutations, including 8 missense mutations, 1 nonsense mutation and 3 splice mutations were found in 24 alleles. The most common mutations were EX6- 96A 〉 G and P281L, which were respectively prevalent in Asia and Europe populations. The common mutations were R243Q, R111 X, R176X and F161S. The mutation frequency of R243Q was the highest and R111X was the third highest in Northern China. R176X and F161S were two rare mutations world wide. Especially, F161S was a Chinese-specific mutation because it was for the second time that it was found in China. The mutations detected in this study were first reported in these 3 minority nationality populations, which showed a distinct ethical characteristic. Conclusions There is not only a consanguineous relation but also a distinct difference in PAH gene distribution between Xinjiang minority nationality population and yellow race and Latin-American. The results suggest that Xinjiang could probably be a special PAH gene distribution region.