叶酰多聚谷氨酸合成酶基因一个新的错义突变的发现

目的：研究叶酰多聚谷氨酸合成酶（FPGS）基因编码区突变及多态性在中国汉族急性白血病（AL）患儿与健康儿童中的频率分布特征，为探讨FPGS 基因多态性与肿瘤化疗个体化用药之间的关系提供理论依据。方法：采用PCR-DGGE结合DNA直接测序的方法对91例AL患儿和124例上呼吸道感染儿童（对照组）的FPGS基因第5号外显子的突变及多态性情况进行分析，计算等位基因频率和基因型频率并分析其差异性。结果：在对照组儿童FPGS编码区中发现了一个国内外未见报道的错义突变502/490 T>C（L151/101P），分别在FPGS线粒体型和胞浆型中发现了新突变2例和3例，并鉴定了其等位基因频率为0.70%（胞浆型）和0.47%（线粒体型）。这个新的错义突变与儿童AL无明显的相关性。结论：首次在中国汉族儿童中发现FPGS外显子5的一个新的错义突变502/490 T>C（L151/101P），其在中国汉族儿童中的等位基因频率为 0.70%（胞浆型）和0.47%（线粒体型）。

A novel missense mutation of folypolyglutamate synthetase gene

Objective To examine allelic frequencies of coding single nucleotide polymorphisms(cSNPs) of folypolyglutamate synthetase(FPGS) gene in Chinese Han children with acute leukemia(AL),in order to provide a basis for detecting the relationship between FPGS genetic polymorphisms and tumor individualized chemotherapy.Methods cSNPs of exon 5 were detected with polymerase chain reaction(PCR)-denaturing gradient gel electrophoresis(DGGE) in 91 children with AL and 124 children with upper respiratory infection as controls.Genotypes and allelic frequencies were examined.Results A novel missense mutation,502/490 T>C(L151/101P),was found in exon 5 of FPGS from control children.The novel mutation was found in mitochondrial variants in two cases and cytosolic variants in three cases.The cytosolic and mitochondrial variants displayed allelic frequencies of 0.70 % and 0.47 % respectively.The novel mutation was not associated with susceptibility to AL.Conclusions A novel missense mutation 502/490 T>C(L151/101P) in exon 5 of FPGS gene is firstly found in Chinese Han children,and the cytosolic and mitochondrial variants display allelic frequencies of 0.70 % and 0.47 % respectively.