摘要
目的为了快速、准确地对黏多糖贮积症Ⅱ型(MPSⅡ)高危胎儿做出产前基因诊断,从而及时而高效地防止病胎的出生。方法在阐明先证者病因及其父母基因型的基础上,采用已建立的突变特异性扩增系统(ARMS)特异引物直接鉴定法、变性高效液相色谱(DHPLC)快速筛检法,结合DNA序列分析法,对已孕20周的高危胎儿的艾杜糖-2-硫酸酯酶(IDS)基因相应突变位点进行快速检测和鉴定。由于MPSⅡ为XR病,故又用SRY引物对胎儿进行性别鉴定,以避免可能出现的母血污染而导致的误诊。结果所怀胎儿未获得母源性的c.1344delA突变,是1例基因型完全正常的女胎。后经随访和复检,证实所生小孩的基因型、表现型都与产前诊断结果完全一致。结论 ARMS特异引物直接鉴定法、DHPLC快速筛检法结合DNA序列分析法是快速、准确产前诊断MPSⅡ高危胎儿的有效方法。其中,所建立的ARMS和DHPLC方法,既快速特异,又简便经济,可在一天之内送报结果 ,特别适用于已明确病因的高危胎儿的早期诊断以及正常组和患者试验组的快速鉴别。这一产前基因诊断工作的成功实施为今后继续开展本病以及其他相关遗传病的遗传咨询、基因诊断和产前诊断积累了宝贵的经验,也为今后开展植入前遗传学诊断等打下较好的基础。
Objective To give a rapid and accurate prenatal diagnosis of MPS Ⅱ high-risk fetus,and prevent birth of ill fetuses promptly and efficiently. Methods On the basis of fully understand of the genotypes of the proband and his parents,relevant gene locus of IDS gene of 20-gestational-week high-risk fetus was determined with established direct ARMS specific primer assay,DHPLC rapid screening assay and DNA sequencing assay. Results The result showed the fetus did not inherit maternal c. 1344 del A mutation,and her genotype is completely normal. The follow-up survey and reexamination confirmed that the genotype and phenotype are exactly in line with the prenatal diagnosis. It demonstrated that direct ARMS specific primer assay,DHPLC rapid screening assay combined with DNA sequencing assay are rapid and accurate prenatal diagnosis methods of MPS Ⅱ. Conclusions The established ARMS and DHPLC assays are rapid,specific and economic,results can be attained in one day. It is especially adequate for early diagnosis of high-risk fetus whose pathogen is known and for rapid differential diagnosis of normal group and patient group. The success of this prenatal diagnosis provide precious experience for future genetic counseling,genetic diagnosis and prenatal diagnosis of MPS Ⅱ and other genetic diseases. It also lays the foundation for future preimplantation genetic diagnosis.
出处
《中华临床医师杂志（电子版）》
CAS
2010年第5期552-557,共6页
Chinese Journal of Clinicians(Electronic Edition)
基金
国家自然科学基金资助项目(30772069)
CMB(2006)部分资助项目
