甲基丙二酸血症患儿MUT基因突变分析  

Analysis of the MUT gene mutations in patients with methylmalonic acidemia

作　　者：王斐[1] 韩连书[1] 叶军[1] 邱文娟[1] 张雅芬[1] 高晓岚[1] 王瑜[1] 杨艳玲[2] 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、遗传代谢病研究室,200092 [2]北京大学第一医院儿科

出　　处：《中华医学遗传学杂志》2009年第5期485-489,共5页Chinese Journal of Medical Genetics

基　　金：基金项目：十一五国家科技支撑计划课题（2006AB105A05,2006BA105A07）;国家高技术发展计划（2007AA022447）;上海市卫生局重大课题（2008ZD001）;上海市卫生局科研课题（2006043）

摘　　要：目的检测甲基丙二酸血症（methylmalonicacidemia，MMA）患儿MUT基因突变类型及突变频率，探讨基因型与临床表型之间的关系。方法依据串联质谱检测血酰基肉碱、气相色谱质谱检测尿甲基丙二酸以及维生素B12负荷试验等，诊断21例单纯MMA患儿；采用聚合酶链反应和直接测序法对这些患儿进行MUT基因突变检测分析。结果在21例单纯MMA患儿中14例检测到17种MUT基因突变，其中8种为未报道突变。以c．323G〉A（R108H）、c.729_730insTT（D244LfsX39）与c.630_1631GG〉TA（G544X）较为常见，突变频率分别为14．3％、10．7％及14．3％，以错义突变多见（64．7％）。14例MUT突变患儿中10例为早发型，1例为迟发型，3例由新生儿出生筛查检出；11例为维生素B12无效型，3例为有效型。结论揭示了中国MMA患儿中MUT基因的部分突变谱，MUT基因突变患儿发病较早，多为维生素B12无效型。Objective To investigate the MUT gene mutations in patients with methylmalonic acidemia （MMA）, and analyze the genotype-phenotype correlation in patients with methylmalonyl-CoA mutase deficiency. Methods The diagnosis of the disease mainly depends on the measurement of C3 （acylcarnitine）, C3/C0 （free carnitine） and C3/C2 （acetylcarnitine） in the blood by tandem mass spectrometry, the detection of methylmalonic acid in the urine by gas-chromatography mass spectrometry, the determination of total homocysteine in the serum, and the loading test of vitamin 812. The entire coding region of the MUT gene was screened by PCR combined with direct DNA sequencing in 21 isolated MMA patients. Novel mutations were identified by restriction fragment length polymorphism （RFLP） and sequence analysis in 100 controls. Results Seventeen MUT gene mutations were detected in 14 of the 21 patients, among them 8 mutations were novel, and R108H, D244LfsX39 and G544X were more frequent, with the frequencies of 9. 5Y0, 7. 1% and 9. 5%, respectively. Most mutations were missense mutations （64.7%）, and majority of them were in exons 2 and 3 （55.6%）. Ten out of the 14 patients with MUT gene mutations had early-onset disease, while one case had late-onset disease, and the remaining 3 cases were detected by newborn screening. In addition, 11 of these 14 patients did not respond to vitamin B12. Conclusion This study revealed partial MUT gene mutation spectrum in Chinese patients with isolated MMA. The patients carrying MUT mutations often had early-onset disease, and most of them were VitB12- non-responsive.

关 键 词：甲基丙二酸 甲基丙二酰辅酶A变位酶 MUT基因 突变 

分 类 号：R686[医药卫生—骨科学]