CAJ | 학술논문

目的确定黏多糖贮积症Ⅱ型(Mucopolysaccharidosis type Ⅱ,MPS Ⅱ)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 high-performance liquid chromatography,DHPLC)在正常人群中进行筛查.结果检测到先证者IDS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IDS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IDS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 IDS基因c.892C>T突变是该MPS Ⅱ患者的主要致病原因;产前诊断证明胎儿为男性患病胎儿.
목적 학정점다당저적증Ⅱ형(Mucopolysaccharidosis type Ⅱ,MPS Ⅱ)일가계적치병기인돌변,병대고위태인진행산전진단.방법 응용취합매련반응화직접측서적방법,대선증자、태인급부분가계성원애두당-2-류산지매(iduronate-2-sulfatase,IDS)기인적소유외현자급기여내함자교계처서렬진행검측;대측서발현적성질미지적감기개변채용고효액상색보기술(denatruring high-performance liquid chromatography,DHPLC)재정상인군중진행사사.결과 검측도선증자IDS기인3개감기개변:5호외현자c.684A>G,6호외현자c.851C>T,7호외현자c.892C>T;선증자모친화외조모적IDS기인존재c.684A>G잡합개변,c.851C>T잡합개변급c.892C>T잡합개변;100례가계외정상남성미발현IDS기인5호외현자c.684A>G화6호외현자c.851C>T적감기개변;태인기인형여선증자상동.결론 IDS기인c.892C>T돌변시해MPS Ⅱ환자적주요치병원인;산전진단증명태인위남성환병태인.
Objective Mucopolysaccharidosis type Ⅱ (MPS Ⅱ) is a lethal, X-linked recessive disorder caused by mutation of iduronate-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 allelic 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 (Ⅵ 11) inherited the same mutation of IDS gene as the proband. Conclusion Mutation c. 892C > T of IDS gene causes MPS Ⅱ in this family and prenatal diagnosis in one affected fetus was achieved.