内蒙古经典型苯丙酮尿症PAH基因外显子7突变的检测及一种新突变的鉴定

DETERMINATION OF EXON 7 MUTATION IN PAH GENE OF CLASSICAL PHENYLKETONURIA AND IDENTIFICATION OF NOVEL MUTATION IN INNER MONGOLIA

目的 :探讨内蒙古地区经典型苯丙酮尿症 (PKU)基因突变特征 ,为基因诊断提供依据。方法 :应用PCR-单链构象多态性分析技术和 DNA直接测序的方法 ,对 2 2例内蒙古地区 PKU病人苯丙氨酸羟化酶(PAH)基因外显子 7内突变进行了检测。结果 :共检出 4种错义突变 :R2 43 Q、R2 5 2 Q、R2 61 Q及 G2 3 9D,1种剪接部位突变 IVS7nt(2 ) ,突变频率分别为 :8/4 4、1 /4 4、1 /4 4、1 /4 4、1 /4 4。经与国际 PAH基因突变数据库比较 ,确认 G2 3 9D(G→ A)为国际上首次发现的新突变。结论 :内蒙古地区 PKU病人 PAH基因外显子 7的突变位点、突变频率和中国东北人群相类似 ,但与中国南方人群 PAH基因突变特点不同 。

Objective: To study phenylketonuria(PKU) gene mutation character in Inner Mongolia area and provide foundation for gene diagnosis. Methods: Exon7 of the phenylalanine hydroxylase(PAH) gene was analyzed in 22 children affected with classical PKU from Inner Mongolia by using PCR-single strand conformation polymorphism (PCR-SSCP) technique and DNA direct sequencing. Results: Four missense mutations(i.e. R243Q, R252Q, R261Q and G239D)and one splice site muation(IVS7nt2) were identified. The mutation frequencies are 8/44,1/44?1/44?1/44?1/44, respectively. The mutation G239D(G→A) was demonstrated as novel mutation in comparison with the PAH mutation database. Conclusion:Mutation and their frequencies in exon7 of PAH gene of PKU in the people of Inner Mongolia are similar to those in the northeastern people, but such characteristic is different from that in the southern people. This finding has theoretical and practical value for increasing gene diagnosis rate in Inner Mongolia.\;