摘要
目的确定黏多糖贮积症Ⅱ型（Mucopolysaccharidosis typeⅡ，MPSⅡ）一家系的致病基因突变，并对高危胎儿进行产前诊断。方法应用聚合酶链反应和直接测序的方法，对先证者、胎儿及部分家系成员艾杜糖-2-硫酸酯酶（iduronate-2-sulfatase，IDS）基因的所有外显子及其与内含子交界处序列进行检测；对测序发现的性质未知的碱基改变采用高效液相色谱技术（denatruring highperformance liquid chromatography，DHPLC）在正常人群中进行筛查。结果检测到先证者／DS基因3个碱基改变：5号外显子c．684A〉G，6号外显子c．851C〉T，7号外显子c．892C〉T；先证者母亲和外祖母的／DS基因存在c．684A〉G杂合改变，c．851C〉T杂合改变及c．892C〉T杂合改变；100例家系外正常男性未发现／DS基因5号外显子c．684A〉G和6号外显子c．851C〉T的碱基改变；胎儿基因型与先证者相同。结论／DS基因c．892C〉T突变是该MPSⅡ患者的主要致病原因；产前诊断证明胎儿为男性患病胎儿。
Objective Mueopolysaccharidosis type Ⅱ （MPS Ⅱ ） is a lethal, X-linked recessive disorder caused by mutation of idnronate-2-sulfatase （ IDS ） gene. Up to now there is no really effective treatment for this disorder, therefore it is important to provide an accurate genetic diagnosis and prenatal diagnosis for the MPS Ⅱ families. In this study, we identify the pathogenic mutation in a Chinese family with MPS Ⅱ. Method The 8 years old male proband from a Chinese family was clinically diagnosed with MPS Ⅱ. There are other 4 patients with similar phenotypes in the family who died at 9, 11, 7 and 10 years of age, respectively. Mutation analysis was carried out by polymerase chain reaction and direct sequencing of all exons and exon/intron boundaries of IDS gene. Denaturing high performance liquid chromatography （DHPLC） analysis was performed to screen the unknown variations of IDS gene in 100 unrelated control males. Result Two allelie variants of exon 5 （c. 684A 〉 G） and exon 6 （c. 851C 〉 T） and a nonsense mutation of exon 7 （ c. 892C 〉 T） were detected in IDS gene of the proband. Heterozygous mutations c. 684A 〉 G, c. 851C 〉 T and c. 892C 〉 T were detected in both proband＇s mother and maternal grandmother. The unknown variations of c. 684A 〉 G and c. 851C 〉 T were not found in the 100 unrelated control males. The male fetus （ Ⅳ 11 ） inherited the same mutation of IDS gene as the proband. Conclusion Mutation c. 892C 〉 T of IDS gent causes MPS Ⅱ in this family and prenatal diagnosis in one affected fetus was achieved.
出处
《中华儿科杂志》
CAS
CSCD
北大核心
2009年第2期109-113,共5页
Chinese Journal of Pediatrics
基金
国家自然科学基金（30571021）
国家“十一五”科技支撑项目（2006BA105A08）
作者简介
通信作者：邬玲仟（Email：wulingqian@sklmg．edu．cn）
