甲基丙二酸血症患儿mut基因两个新遗传突变的发现和鉴证  

Molecular analysis of two novel mut gene mutations in Chinese patient with methylmalonic academia

作　　者：常会波[1] 吴建新[1] 刘哲伟[2] 王立文[3] 许克铭[3] 张宇[1] 李媛媛[1] 张霆[2] 

机构地区：[1]首都儿科研究所生化室,北京100020 [2]首都儿科研究所分子免疫室,北京100020 [3]首都儿科研究所神经内科,北京100020

出　　处：《中华神经科杂志》2006年第11期742-744,共3页Chinese Journal of Neurology

基　　金：国家重点基础研究发展规划资助项目(2001CB510306);北京市优秀人才培养专项经费资助项目

摘　　要：目的研究甲基丙二酸血症患儿甲基丙二酰辅酶A变位酶基因(mut)变异,鉴证和分析突变位点。方法通过聚合酶链反应(PCR)对14例患儿、部分直系亲属及健康对照的mut基因外显子进行扩增和测序。采用限制性片段长度多态性方法进行变异位点鉴证。利用软件对甲基丙二酰辅酶A变位酶蛋白三维结构进行模拟分析。结果在例1的mut基因第3号外显子,发现D147E(cDNA517T→A)和244insL(cDNA805insTT)两处杂合突变,分别来自例1的母亲和父亲。D147E处于保守氨基酸区域,244insL移码突变导致终止密码子提前出现。结论中国甲基丙二酸血症患儿mut基因出现两个新的遗传突变D147E和244insL。Objective To identify and analyze the mutation types of mut gene in methylmalonic acidemia （MMA） patient. Methods Genomic DNA was amplified by PCR using oligonucleotide primers. The PCR products of mut gene was analyzed by sequencing. PCR/RFLP method was used to analyze the mutations of mut gene. The three-dimensional structure of one subunit of the human methylmalonyl-CoA model was deduced. Results The D147E（cDNA 517T→A）and 244insL（cDNA 805insTF） were detected at exon 3 as two kinds of heterozygous mutation in the patient 1, originating from his mother and the father respectively, as proven by PCR/RFLP analysis. D147E was a conservative amino acid. 244insL, a frameshifi mutation, resulted in the appearance of terminator codon in advance. Conclusion We have firstly detected two novel mutations： D147E and 244insL in Chinese patient with methylmalonic acidemia.

关 键 词：甲基丙二酸 突变 甲基丙二酸单酰CoA 变位酶 

分 类 号：R725.9[医药卫生—儿科]