摘要目的 分析1例MELAS综合征线粒体基因组突变情况.方法 2012年11月北京大学第一医院儿科临床拟诊为MELAS的1例男性患儿,详细收集该患儿临床资料,排除常见线粒体点突变(如A3243G、A8344G、T8993G/C、G13513A等)后,应用聚合酶链式反应-直接测序法分析16.6 kb的线粒体基因组全序列,并应用聚合酶链式反应-限制性片段长度多态性分析(PCR-RFLP)对突变进行验证.结果 经线粒体基因组全测序后,在患者的外周血和尿沉渣线粒体DNA (mtDNA)均检测出G14453A点突变,父母及100名健康对照的外周血mtDNA未发现携带此突变.经PCR-RFLP方法验证,患者外周血mtDNA中G14453A突变比例为56.8％,尿沉渣mtDNA中G14453A突变比例为72.5％.患者线粒体呼吸链复合物Ⅰ活力降低,为67.6 nmol·min-1·mg-1.参考www.mitomap.org网站及NCBI数据库,本例mtDNA G14453A突变所致MELAS综合征为国内首次报道.结论 G14453A突变是导致MELAS综合征的致病突变之一,发病机制有待进一步研究.

abstractsObjective To analyz mitochondrial DNA mutation in one case of mitochondrial myopathy,encephalopathy,lactic acidosis and stroke-like episodes (MELAS).Methods The patient,a 10-years-old boy,clinically diagnosed as MELAS.The clinical information was collected,and the normal mitochondrial mutations (such as A3243G,A8344G,T8993G/C,G13513A etc)were excluded.PCR-sequencing was used to analyz the whole-mitochondrial genome(16.6 kb),and PCR-RFLP was used to confirm the mutations.Results m.G14453A mutation was detected from the patient's peripheral blood and urine,but it was not found in his parents and 100 normal controls.The m.G14453A mutation was confirmed by PCR-RFLP,and mutation ratio of in blood was 56.8％ and urine was 72.5％.The activity of complex Ⅰ was decreased(67.6 nmol · min-1 · mg-1).This was the first report that m.G14453A mutation could lead to MELAS in China according www.mitomap.org web and NCBI.Conclusion m.G14453A mutationis one of the causative mutations in MELAS,but the mechanism of the mutation should be studied in future.