55例6-丙酮酰四氢蝶呤合成酶缺乏症基因突变分析  

Mutational analysis of patients with 6-pyruvoyltetrahydrobiopterin synthesis deficiency

作　　者：顾梅青[1] 叶军[1] 邱文娟[1] 韩连书[1] 张雅芬[1] 顾学范[1] 

机构地区：[1]上海交通大学医学院附属新华医院,上海市儿科医学研究所内分泌遗传代谢病室,200092

出　　处：《中华医学遗传学杂志》2009年第2期183-186,共4页Chinese Journal of Medical Genetics

基　　金：上海市重点学科建设项目（T0204）;国家高技术研究发展计划（2007AA022447）;“十一五”国家科技支撑计划课题（2006BA105A05,2006BA105A07）

摘　　要：目的 了解中国大陆6-丙酮酰四氢蝶呤合成酶缺乏症（6-pyruvoyltetrahydrobiopterin synthesis 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％）、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。Objective To determine the gene mutation spectrum of patients pyruvoyltetrahydrobiopterin synthesis deficiency （PTPSD） in China's Mainland. Methods with 6 The 6 pyruvoyltetrahydrobiopterin synthesis gene （PTS） was analyzed in 55 PTPSD patients by using PCR- restriction 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 IVSlnt-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, MSOT, 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.

关 键 词：高苯丙氨酸血症 四氢生物蝶呤缺乏症 6-丙酮酰四氢蝶呤合成酶基因 突变 

分 类 号：R686[医药卫生—骨科学]