一例Morquio A综合征高危胎儿的快速产前基因诊断  

Rapid prenatal genetic diagnosis of a fetus with a high risk for Morquio A syndrome

作　　者：郭奕斌[1] 艾阳[1] 赵燕[1] 唐佳[1] 蒋玮莹[1] 杜敏联[2] 马华梅[2] 钟燕芳[3] 

机构地区：[1]中山大学中山医学院医学遗传学教研室,广州510080 [2]中山大学中山医学院附属第一医院儿科,广州510080 [3]广东省妇幼保健院产前诊断中心

出　　处：《中华医学遗传学杂志》2012年第2期126-130,共5页Chinese Journal of Medical Genetics

基　　金：基金项目：国家自然科学基金（30772069）

摘　　要：目的快速、准确地对MorquioA综合征[又称黏多糖贮积症ⅣA型（mucopolysaccharidosis type ⅣA，MPSⅣA）]高危胎儿做出产前基因诊断，从而及时而高效地防止患儿的出生，以最大程度减少流产对母体的伤害。同时，为今后的植入前遗传学诊断（preimplantation genetic diagnosis，PGD）创造必要的前提条件。方法在明确先证者病因及其父母基因型的基础上，应用已建立的突变特异性扩增系统（amplification refractor ymutation system，ARMS）直接鉴定法、变性高效液相色谱（denaturing high performance liquid chromatography，DHPLC）快速筛检法，结合DNA序列分析法，对1例已孕10周的MPSIVA高危胎儿的GALNS基因相应突变位点进行快速检测和鉴定。结果胎儿的DHPLC筛检结果显示第1外显子和第10外显子的PCR产物都有异常双峰，而相应正常对照均只有正常单峰；用GALNS基因ARMS特异引物扩增的结果显示：胎儿有相应的特异扩增产物，而正常对照无；普通引物扩增产物的测序结果显示：胎儿GALNS基因的第1外显子和第10外显子分别获得了父源性的c．106—111del（p．L36-L37del）杂合缺失突变和母源性的c．1097T〉C（P．L366P）杂合错义突变，为两种突变的复合杂合子。结论该高危胎儿是一带有与先证者完全相同基因型的MorquioA综合征病胎，应尽早终止妊娠；ARMS法、DHPLC法结合DNA序列分析法是快速、准确产前基因诊断MPSⅣA高危胎儿的有效方法，特别适用于已明确病因的高危胎儿的早期诊断；其中，ARMS法和DHPLC法还特别适用于大批量正常对照组的快速鉴别，对于新突变的致病性鉴定起着重要的作用。Objective To provide rapid and accurate prenatal genetic diagnosis for a fetus with high risk of Morquio A syndrome. Methods Based on ascertained etiology of the proband and genotypes of the parents, particular mutations of the GALNS gene were screened at 10th gestational week with amplification refractory mutation system （ARMS）, denaturing high performance liquid chromatography （DHPLC）, and direct DNA sequencing. Results DHPLC screening has identified abnormal double peaks in the PCR products of exons 1 and 10, whilst only a single peak was detected in normal controls. Amplification of ARMS-specific primers derived a specific product for the fetus＇ s gene, whilst no similar product was detected in normal controls. Sequencing of PCR products confirmed that exons 1 and 10 of the GALNS gene from the fetus contained a heterozygous paternal e. 106-111 del （p. L36-L37 del） deletion and a heterozygous maternal c. 1097 T〉C （p. L366P） missense mutation, which resulted in a compound heterozygote status. Conclusion The fetus was diagnosed with Morquio A syndrome and a genotype similar to the proband. Termination of the pregnancy was recommended. Combined ARMS, DHPLC and DNA sequencing are effective for rapid and accurate prenatal diagnosis for fetus with a high risk for Morquio A syndrome. Such methods are particularly suitable for early diagnosis when pathogenesis is clear. Furthermore, combined ARMS and DHPLC are suitable for rapid processing of large numbers of samples for the identification of new mutations.

关 键 词：Morquio A综合征 GALNS基因 产前基因诊断 突变特异性扩增系统 变性高 效液相色谱 DNA序列分析 

分 类 号：R714.5[医药卫生—妇产科学]