新疆苯丙酮尿症患者苯丙氨酸羟化酶基因第11、12外显子点突变分析

Studies on mutations of exon 11 and 12 in phenylalaninase gene of phenylketonuria patients in Xinjiang

目的分析新疆地区苯丙酮尿症(PKU)患者中苯丙氨酸羟化酶(PAH)基因第11、12外显子点突变。方法应用PCR及单链构象多态性(SSCP)分析技术结合基因序列测定方法进行筛查和鉴定。结果在37例PKU患者共74条染色体中,检出基因突变5种,其中第11外显子2种,即无义突变Y356X和剪接位点突变V399V,突变发生率分别为5.4%和5.4%,外显子11的等位基因频率是10.8%;第12外显子3种,全部为错义突变,分别是R413P、R408W及A434D,其突变发生率为4.1%、1.4%和1.4%,外显子12的等位基因频率占6.8%。上述突变中,R413P以日本人最为常见,Y356X和V399V多集中于我国北方地区,而R408W则是欧美及拉美等国最多见的基因突变。结论新疆地区是中国与亚欧地区之间一个较为特殊的PAH突变基因分布带,具有明显的地域特征。

Objective To investigate the point mutation features of exon 11 and 12 in phenylalanine hydroxylase（PAH）gene of the patients with phenylketonuria（PKU）in Xinjiang. Methods FCR/SSCP and gene sequencing were used in present study. Results Five mutations were identified from 74 chromosomes of 37 patients. Among them two mutations were detected from exon 11 including nonsense mutation Y356X and splice site mutation V399V, and three mutations were detected from exon 12 including R413P, R408W and A434D, all which were missense mutation. The frequency of the five mutations were 5. 4%, 5.4%, 4. 1%, 1.4%, 1.4% and 1.4%, respectively. The aUelomorphic frequency of exon 11 and 12 were 10. 8% and 6.8%, respectively. Among the five mutations, R413P is common in Japan, Y356X and V399V are centered in north China, and R408W is the most often mutation in Europe and America. Conclusion Xinjiang Uygur Autonomous Region is situated on northwest China, contiguous to other countries of eentral Asia, and is such an area differed from other areas of China, and distributed special PAH gene mutation in PKU patients.