55例6-丙酮酰四氢蝶呤合成酶缺乏症基因突变分析

目的 了解中国大陆6-丙酮酰四氢蝶呤合成酶缺乏症(6-pyruvoyltetrahydrobiopterinsynthesis deficiency,PTPSD)基因突变谱.方法 采用PCR-限制性长度多态性及常规基因测序法,对55例PTPSD进行6-丙酮酰四氢蝶呤合成酶基因(6-pyruvoyltetrahydrobiopterin syntheie gene,PTS)检测以得出基因突变类型和频率.寻找热点突变;分析基因型与临床表型的关系.结果 PTS基因突变检出率95.28%,检出18种突变类型.P87S(40.57 0A)、N52S(13.21%)、D96N(12.26%)及IVSInt-291A>G(10.38%)为热点突变,前3种突变导致严重型PTPSD.P87L为国内首次报道,发现5种新突变(Q13X、M80T,IVS4nt-2A>G、L93M、K131N).结论 N52S、P87S、D96N及IVSInt-291A>G为中国人PTS的热点突变,PCR-限制性长度多态性方法进行热点突变筛检可提高基因诊断效率.

Mutational analysis of patients with 6-pyravoyltetrahydrobiopterin synthesis deficiency

Objective To determine the gene mutation spectrum of patients with 6pyruvoyltetrahydrobiopterin synthesis deficiency (PTPSD) in Mainland China. Methods The 6pyruvoyltetrahydrobiopterin synthesis gene (PTS) was analyzed in 55 PTPSD patients by using PCRrestriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing. The relationship between the genotype and phenotype was analyzed. Results Eighteen mutations were identified and the detection rate of gene mutation was 95.28%. Four hot-spot mutations, namely P87S(40.57%), N52S (13.21%), D96N(12.26%) and IVSInt-291A>G(10.38%) were found in this study, and the first three were associated with severe phenotype. The P87L was reported firstly in Chinese patients, and the Q13X, M80T, IVS4nt-2A>G, L93M and K131N were novel mutations. Conclusion The P87S, N52S, D96N and IVSInt-291A>G mutations are the hot-spots mutations of the PTS gene in Chinese PTPSD patients. Using PCR-RFLP technique to screen the mutations in the PTS gene can increase the efficiency of gene diagnosis.