艾杜糖-2-硫酸酯酶活性测定在黏多糖贮积病Ⅱ型产前诊断中的应用  

Quantification of the iduronate-2-sulfatase activity in prenatal diagnosis of mucopolysaccharidosis typeⅡ

作　　者：赵小媛[1] 张文[1] 黄永兰[2] 苏雪莹 李秀珍[1] 盛慧英[1] 曾春华 尹曦[1] 刘宗才 蔡燕娜[1] 刘丽[1] Zhao Xiaoyuan;Zhang Wen;Huang Yonglan;Su Xueying;Li Xiuzhen;Sheng Huiying;Zeng Chunhua;Yin Xi;Liu Zongcai;Cai Yanna;Liu Li(Department of Genetics and Endocrinology,Guangzhou Women and Children′s Medical Center Affiliated to Guangzhou Medical University,Guangzhou 510623,China;Newborn Screening Center,Guangzhou Women and Children′s Medical Center Affiliated to Guangzhou Medical University,Guangzhou 510623,China)

机构地区：[1]广州医科大学附属广州市妇女儿童医疗中心遗传与内分泌科,广州510623 [2]广州医科大学附属广州市妇女儿童医疗中心新生儿筛查中心,广州510623

出　　处：《中华实用儿科临床杂志》2022年第24期1879-1882,共4页Chinese Journal of Applied Clinical Pediatrics

基　　金：广东省省级科技计划项目(2011B61300086)。

摘　　要：目的评估黏多糖贮积病Ⅱ型(MPSⅡ)高危孕妇胎儿绒毛和孕妇外周血血浆艾杜糖-2-硫酸酯酶(IDS)活性以及基因分析在MPSⅡ产前诊断中的应用。方法回顾性分析2013年2月至2020年12月在广州市妇女儿童医疗中心进行产前诊断的23例MPSⅡ高危孕妇的酶学检测及基因分析结果,采用人工底物荧光法检测胎儿绒毛(30例)和血浆(28例)IDS酶活性,以非高危妊娠孕妇的28例绒毛和34例血浆检测值为对照,绒毛同时送检基因检测和胎儿性别鉴定。组间比较采用独立样本t检验。结果非MPSⅡ高危孕妇胎儿绒毛和血浆IDS活性正常参考值为绒毛(71.2±23.4)nmol/(mg·4 h),血浆(611.1±114.5)nmol/(mL·4 h);30例高危胎儿绒毛中8例男性受累胎儿绒毛IDS酶活性为(1.7±0.3)nmol/(mg·4 h),显著低于11例男性非受累胎儿[(83.2±6.3)nmol/(mg·4 h)]和9例女性非携带者胎儿[(80.0±7.5)nmol/(mg·4 h)](t=10.8、8.8,均P<0.01)。28份MPSⅡ高危孕妇外周血血浆IDS酶活性中8例受累男性胎儿孕母外周血IDS酶活性(225.4±20.5)nmol/(mL·4 h),显著低于男性胎儿非受累孕母IDS酶活性[(451.0±15.1)nmol/(mL·4 h)]和女性非携带者胎儿孕母IDS酶活性[(467.7±45.3)nmol/(mL·4 h)]。30例MPSⅡ高危胎儿绒毛中找到已知致病性突变8例,突变位点分别为c.1048A>C、c.212G>A、c.514C>T、c.257C>T、c.425C>T、c.998C>T,其中6例IDS酶活性显著降低,均为男性受累胎儿,另2例IDS酶活性正常,为女性携带者胎儿。结论孕妇外周血血浆与绒毛IDS酶活性及基因结果有很好的相符性,对孕早期产前诊断MPSⅡ有重要参考价值;当先证者未找到基因突变或新突变的致病性尚不清楚时可单独检测绒毛酶活性进行产前诊断MPSⅡ。Objective To evaluate the activity of iduronate-2-sulfatase(IDS)in fetal villi and peripheral blood plasma of pregnant women at high risk of mucopolysaccharidosis typeⅡ(MPSⅡ),and to discuss the application of gene analysis in prenatal diagnosis of MPSⅡ.Methods The enzymatic testing and gene analysis results of 23 pregnant women at high risk of MPSⅡ,who underwent prenatal diagnosis in Guangzhou Women and Children′s Medical Center from February 2013 to December 2020,were analyzed retrospectively.The IDS activity in fetal villi(30 cases)and plasma(28 cases)was detected by artificial substrate fluorescence.The IDS activity in fetal villi(28 cases)and plasma(34 cases)of normal pregnant women was taken as control.Meanwhile,the fetal villi of both pregnant women at high risk of MPSⅡand normal pregnant women were also analyzed by gene testing and for fetal sex identification.Data were compared between groups by the independent samples t test.Results The normal reference values of the IDS activity in fetal villi and plasma of normal pregnant women were(71.2±23.4)nmol/(mg·4 h)and(611.1±114.5)nmol/(mL·4 h),respectively.Among the 30 cases of high-risk fetal villi,the IDS activity in fetal villi of 8 affected male fetuses was(1.7±0.3)nmol/(mg·4 h),which was significantly lower than that of 11 unaffected male fetuses(83.2±6.3)nmol/(mg·4 h)and that of 9 non-carrier female fetuses(80.0±7.5)nmol/(mg·4 h)(t=10.8,8.8;all P<0.01).Meanwhile,the IDS activity was measured in the maternal peripheral plasma of 28 pregnant women at high risk of MPSⅡ.Among them,the IDS activity in 8 affected male fetuses was(225.4±20.5)nmol/(mL·4 h),which was significantly lower than that in non-affected male fetuses[(451.0±15.1)nmol/(mL·4 h)]and that in non-carrier female fetuses[(467.7±45.3)nmol/(mL·4 h)].Eight known pathogenic mutations were found in 30 cases at high risk of MPSⅡof fetal villi,and the mutation types were c.1048A>C,c.212G>A,c.514C>T,c.257C>T,c.425C>T,and c.998C>T.Of the 8 cases,6 affected male fetuses had

关 键 词：黏多糖贮积症Ⅱ型 产前诊断 艾杜糖-2-硫酸酯酶 

分 类 号：R714.5[医药卫生—妇产科学]