云南地区汉族苯丙酮尿症患者苯丙氨酸羟化酶基因突变的研究

Mutations of phenylalanine hydroxylase gene detected in 20 patients with phenylketonuria from Yunnan Province

目的探讨云南地区苯丙酮尿症患者苯丙氨酸羟化酶基因突变的特点。方法采集20例患者的血样并提取基因组DNA，对PAH基因的13个外显子及侧翼序列进行Sanger测序以检测突变。结果共发现致病突变15种，根据其构成比的高低分别为p．R243Q（27．5％）、p．Y356X（10．0％）、p．R111X（7．5％）、IVS4＋2T〉A（7．5％）、p．V399V（7．5％），主要涉及外显子7、11、3和内含子4、11的剪切位点。共发现数据库中未收录的突变6种，包括错义突变1种（c．59A〉C、c．60G〉C）（p．Q20P）；插入突变2种：c．690-691insG（S231fsX51）和c．1119-1120insT（1374fsX20）；剪接突变3种：c．441＋2T〉A（IVS4＋2T〉A）、c．842＋4A〉T（IVs7＋4A〉T）和c．1200＋1T〉G（IVS11＋1T〉G）。结论云南地区汉族PAH基因突变特点与中国北方人群较相似，以p．R243Q突变占首位，但其他突变类型及频率具有一定的地域特异性。

Objective To investigate the mutations of phenylalanine hydroxylase （PAH） gene in 20 phenylketonuria （PKU） patients from Yunnan. Methods The 13 exons and the splicing regions of 12 introns of the PAH gene were sequenced to detect mutations in 20 unrelated PKU patients. Results PAH gene sequencing has revealed 15 types of mutations, in which the most frequently mutation was p. R243Q （30.0%）, followed by p. Y356X（10.0%）, p. R111X （7. 5%）, IVS4＋2T〉A （7. 5%） and p. V399V （7.5%）. Exons 7, 11, 3 and introns 4, 11 were most frequently involved. Six novel mutations, including c. 59A〉C, c. 60G〉C, c. 690-691insG, c. 1119-1120insT, c. 441＋2T〉A, c. 842＋4A〉T and c. 1200＋1T 〉G were detected. Conclusion PAH gene mutations identified in Yunnan are more similar to those of northern China, with R243R being the most common, though there are still certain characteristics for the type and frequency of mutations.