一个单纯性甲基丙二酸血症家系中MUT基因两个新突变的鉴定  

Identification of two novel mutations of MUT gene in a Chinese family affected with isolated methylmalonic acidemia

作　　者：谢波波[1] 罗静思[1] 范歆[1] 陈荣誉[1] 王锦[1] 张淑杰[1] 李旺[1] 陈少科[1] 

机构地区：[1]广西壮族自治区妇幼保健院/妇产医院遗传代谢中心实验室,南宁530000

出　　处：《中华医学遗传学杂志》2016年第2期135-139,共5页Chinese Journal of Medical Genetics

基　　金：十二五国家科技支撑计划（2012BAI09B00）

摘　　要：目的对一个单纯性甲基丙二酸血症（methylmalonicacidemia，MMA）家系进行基因突变的检测和分析，探讨其发病的分子遗传学病因。方法PCR结合Sanger测序方法对先证者MUT、MMAA、MMAB3个基因的全部外显子及其旁侧序列进行分析，鉴别其中可能存在的基因突变。采用Polyphen2、SIFT、HSF、DNAMAN6．0和Swiss—PdbViewer4．1．0等软件对检测到的新的基因突变进行致病性分析。结果先证者MUT基因检测到两个杂合突变，分别为C．581C〉T（p．P194L）和c．1219A〉T（p．N407Y），家系分析显示，前者遗传于母亲，后者遗传于父亲。Polyphen2和SIFT软件预测这两个突变均可能致病。这两个位点所在的密码子在不同物种间高度保守，均位于MCM结构的底物结合区——（β，α）8barrel结构域，这两个突变可能通过影响MCM空间构象，从而影响蛋白质的功能。结论两个新的MUT基因突变可能是导致单纯性甲基丙二酸血症的致病原因。Objective To explore the molecular etiology for a Chinese family affected with isolated methylmalonic acidemia （MMA）. Methods Potential mutations of MUT, MMAA and MMAB genes in the proband were screened by PCR and Sanger sequencing. The pathogenicity of identified mutations was analyzed using Polyphen2, SIFT, HSF, DNAMAN 6. 0 and Swiss-PdbViewer4. 1. 0 software. Results Two novel mutations of the MUT gene, including c. 581C〉T （p. P194L） and c. 1219A〉T （p. N407Y）, were discovered in the proband, which were inherited respectively from his mother and father. Bioinformatics analysis suggested that both mutations were damaging. The affected codons P194 and N407, both located in the （β, α）8 barrel domain and to which the substrate methylmalonyl-CoA is bound, are highly conserved across various species. Both mutations can disrupt the space conformation of its protein product, affecting the function of the MCM protein. Conclusion The novel mutations of MUT gene probably underlie the isolated MMA in this family.

关 键 词：甲基丙二酸血症 MUT基因 突变 蛋白质 

分 类 号：R596.1[医药卫生—内科学]