八例戊二酸尿症Ⅰ型患者的GCDH基因突变分析  

Mutation analysis of GCDH gene in eight patients with glutaric aeiduria type Ⅰ

作　　者：陈靖[1] 王朝霞[1] 张锦丽 杨艳玲[2] 陈静[1] 黄一宁[1] 

机构地区：[1]北京大学第一医院神经内科,100034 [2]北京大学第一医院儿科,100034 [3]解放军263医院神经内科

出　　处：《中华医学遗传学杂志》2011年第4期374-378,共5页Chinese Journal of Medical Genetics

摘　　要：目的分析8例戊二酸尿症Ⅰ型（glutaric aciduria typeⅠ，GA-1）患者的GCDH基因突变情况。方法对8例经尿液及血液生化检查诊断为GA-1的患者及其部分家系成员，采集外周静脉血，应用蛋白酶K-盐析法提取DNA，PCR产物直接测序法，进行GCDH基因的所有外显子及侧翼序列的突变筛查。结果8例GA-1患者中，7例为经典的婴幼儿发病，1例为成年晚发型。基因分析证实8例先证者均存在GCDH基因突变，其中5例为复合杂合性突变，符合隐性遗传；另3例只发现1个杂合性突变位点。共发现9种突变类型，其中c．148T〉C、c．371G〉A、909delC和c．263G〉A是4个新的突变位点。结论首次在国内报道8例GA-1患者携带GCDH基因突变，其中1例为罕见的成年晚发型。发现了4个新的突变位点，丰富了GCDH基因的突变谱。Objective To investigate the mutations of glutaryl-CoA dehydrogenase （GCDH） gene in patients with glutaric aeiduria type Ⅰ （GA-1）. Methods Genomic DNA was extracted from peripheral blood cells of the eight probands with GA-1 who were diagnosed by urine and blood analyses. By PCR and direct sequencing, all 11 exons and their flanking sequences of the GCDH gene were examined. Mutation search was also performed in some of their family members. Results Among the eight patients diagnosed by metabolic screening, seven patients belonged to classical infantile-onset. One patient, however, was adult- onset, who was admitted to the hospital because of suffering from ischemic cerebral stroke. The GCDH gene mutations were identified in all the eight probands with GA-1 ： five of them had compound heterozygous mutations, while the other three harbored only one heterozygous mutation. Totally, nine different mutations of the GCDH gene were identified in the eight probands, four of them were novel, i. e. , c. 148T〉C, c. 371G〉A, 909delC and c. 263G〉A. Conclusion GCDH gene mutations are identified in 8 patients with GA-1 in China's Mainland, including one adult patient with late onset. Four novel mutations of GCDH gene are found which expanded the mutational spectrum of the GCDH gene.

关 键 词：戊二酸尿症Ⅰ型 戊二酰辅酶A脱氢酶基因 突变 

分 类 号：R725.8[医药卫生—儿科]