山东省临沂地区苯丙酮尿症患儿苯丙氨酸羟化酶基因突变的特点

Characteristics of phenylalanine hydroxylase gene mutations among patients with phenylketonuria from Linyi region of Shandong Province

目的探讨山东省临沂地区苯丙酮尿症（phenylketonuria，PKU）患儿基因突变的特点，构建该地区苯丙氨酸羟化酶（phenylalanine hydroxylase, PAH）基因的突变谱。方法应用Sanger测序法对51例PKU患儿及其父母PAH基因的全部13个外显子及侧翼的内含子区域进行序列分析。结果在51例患儿的102个等位基因中，共检测到102个突变位点，共31种突变。常见的突变依次为R243Q（17／102，16．67％）、IVS4-1G〉A（9／102，8．82％）、R241C（8／102，7．84％）、R111X（8／102，7．84％）、以及V399V（8／102，7．84％）。D101N、345—347dei突变既往未见报道。突变的类型包括错义突变（19种）、无义突变（4种）、缺失突变（4种）、剪接突变（4种），主要集中在第7（29，28．43％）、第11（18，17．65％）、第3（16，15．69％）和第12（13，12．75％）外显子。结论临沂地区PAH基因的突变主要集中于第7、11、3外显子中，其中突变频率最高者为R243Q。发现了两个新的突变位点，即D101N、345—347del。

Objective To explore the characteristics of PAH gene mutations among patients with phenylketonuria （PKU） from Linyi area of Shandong Province. Methods For 51 children affected with PKU and their parents, the 13 exons and their flanking intronic sequences of the PAH gene were directly sequenced with Sanger method. Results PAH gene mutations were detected in all of the 102 alleles of the patients, which included 31 types of mutations. Common mutations included R243Q （17/102, 16.67%）, IVS4-1G〉A （9/102, 8.82%）, R241C （8/102, 7.84M）, RlllX （8/102, 7.84%）, and V399V （8/102, 7.84%）. In addition, two novel mutations, D101N, 345-347del, have been detected. The 31 types of mutations included missense, nonsense, deletion, and splicing mutations, which were mainly located in exons7 （29, 28. 43%）, 11 （18, 17. 65%）, 3 （16, 15. 69%） and 12 （13, 12. 75%）. Conclusion Mutations of the PAH gene in Linyi region mainly distributed in exons 7, 11, and 3, and the most common mutation were R243Q. Two novel mutations, D101N and 345-347del, have been detected.