内蒙古地区汉族PKU患儿苯丙氨酸羟化酶基因突变分析

Analysis of mutation in phenylalanine hydroxylase gene in the Han ethnic group in Inner Mongolia

目的分析内蒙古地区汉族苯丙酮尿症(PKU)患儿苯丙氨酸羟化酶(PAH)基因的突变频率和特征。方法收集2015年1月至2018年10月在内蒙古自治区妇幼保健院经新生儿疾病筛查及遗传咨询门诊确诊的26例PKU患儿为研究对象,采用PCR直接测序法对26例患儿及其父母的PAH基因第1~13外显子区域进行突变分析。结果共检出24种突变类型,主要以错义突变(66.7%)、剪接突变(20.8%)和无义突变(8.3%)为主,大部分突变集中在第7、11、6、12、3外显子及第12、4内含子区域,最常见的错义突变为R243Q(13.5%)、R241C(5.8%)、Y204C(5.8%)和R413P(5.8%);最常见的剪接突变为IVS12+6T>A(5.8%);最常见的无义突变为Y356X(9.6%);Q355H和c.1316-286A>C是国际上未见报道的新突变。内蒙古地区汉族PKU患儿PAH基因突变构成不同于西北五省,Y204C和IVS12+6T>A在西北五省中均未检出,而在西北五省中突变频率较高的EX6-96A>G在内蒙古地区汉族中未检出。结论内蒙古地区汉族PKU患儿PAH基因突变具有独特的多样性和复杂性。

Objective To investigate frequency and characteristics of phenylalanine hydroxylase(PAH) gene mutation in the Han ethnic children with phenylketonuria(PKU) in Inner Mongolia Autonomous Region.Methods 26 Han ethnic PKU children who were determined a PKU diagnosis in neonatal disease screening and the genetic consultation clinic of Inner Mongolia Maternity and Child Health Hospital from January 2015 to October 2018 were selected.Mutations in exons 1~13 and their flanking intronic region of the PAH gene of 26 children and their parents were analyzed by polymerase chain reaction(PCR) and direct DNA sequencing method.Results A total of 24 different mutations,mainly including missense mutation(66.7%),splicing mutation(20.8%) and nonsense mutation(8.3%) were detected.Most mutations existed centrally in exons 7,11,6,12 and 3 and introns 12 and 4 of PAH gene.The most common missense mutations were R243 Q(13.5%),R241 C(5.8%),Y204 C(5.8%) and R413 P(5.8%).The most common splicing mutation was IVS12+6 T>A(5.8%).The most common nonsense mutation was Y356 X(9.6%).Two novel mutations Q355 H and c.1316-286 A>C were found.The mutation spectrum of PAH gene in the Han ethnic PKU children in Inner Mongolia autonomous region was different from that in all five provinces of northwest China.Y204 C and IVS12+6 T>A had not been detected in any five northwest provinces,and EX6-96 A>G that presented higher mutation detection frequency in the five northwest provinces had not been detected in Inner Mongolia autonomous region yet.Conclusion The mutations of PAH gene in the Han ethnic children in Inner Mongolia are of unique diversity and complexity.