PCR-短串联重复法快速产前筛查唐氏综合征的应用价值  

Practicality of rapid prenatal screening for Down syndrome with PCR-short tandem repeat method

作　　者：管立学[1] 任翠爱[2] 李海波[1] 高丽[3] 贾南[4] 管晖[4] 

机构地区：[1]山东省潍坊市人民医院干细胞实验室,261041 [2]山东省潍坊市人民医院血液科,261041 [3]山东省潍坊市人民医院肿瘤内科,261041 [4]潍坊医学院

出　　处：《中华医学遗传学杂志》2013年第3期277-282,共6页Chinese Journal of Medical Genetics

基　　金：基金项目：山东省卫生科技发展计划项目（2009HW097）

摘　　要：目的探讨PCR短串联重复（PCR—shorttandemrepeat，PCR—STR）法快速产前筛查唐氏综合征（Downsyndrome，DS）的应用价值及7个STR位点多态性分布特点。方法选择21号染色体核心区域（21q22．1—21q22．2）及其附近的7个STR位点（D21S11、D21S1411、D21S1412、D21S1413、D21S1414、D21S1432、D21S2039），应用PCR—STR扩增对978例高危孕妇羊水样本和82例疑似DS患者外周血样本进行基因诊断筛查检测，并与细胞培养染色体核型分析结果比较。结果（1）978例羊水和82例外周血样本PCR-STR检测全部成功，7个STR位点多态信息联合分析，以检出2个位点面积比或强度为1：1：1三条带；或1个位点1：1：1三条带，同时有2个位点面积比或强度为1：2或2：1两条带为DS基因诊断标准，共检出DS阳性40例，其中羊水14例阳性，外周血26例阳性。（2）羊水细胞培养染色体核型分析成功961例（98．3％），17例培养失败（1．7％），检出异常染色体核型44例（4．6％），其中14例为DS核型，包括12例标准DS核型，1例易位DS核型，1例嵌合DS核型。17例培养失败羊水经脐带血染色体分析证实均为正常核型。（3）82例可疑DS患者外周血培养全部成功，检出异常染色体核型30例（36．6％），其中26例为DS核型，包括22例标准DS核型，4例易位DS核型；其它异常核型4例。（4）PCR—STR法对7个STR位点联合分析，单例样本可检出1～4个位点为1：1：1三条带，或可见2～4个位点为面积比率或强度比为2：1或1：2的两条带。羊水和外周血样本DS基因诊断结果与细胞培养染色体核型分析诊断结果完全一致，PCR—STR法快速产前基因诊断DS筛查的灵敏度为100％，未发现假阳性和假阴性结果。（5）7个STR位点杂合率在0．624～0．812，D21S2039和D21S1412位点杂合度最高（〉0．80），D21S1411和D21S1432位点杂合度较低（d0．70）。D21S11和D21S2039位点检出1�Objective To assess the practicality of rapid prenatal screening for Down syndrome （DS） by polymerase chain reaction-short tandem repeat （PCR-STR） method, and to determine the genotypes of 7 STR loci in ethnic Chinese Han from Weifang region. Methods Seven STR markers （D21Sll, D21S1411, D21S1412, D21S1413, D21S1414, D21S1432 and D21S2039） from chromosome 21q22.1-22.2 region were selected. Amniotic samples from 978 high-risk pregnancies and peripheral blood samples from 82 patients suspected with DS were tested with PCR-STR. And the results were verified with G-banding analysis. Results （1） All of the 1 0 6 0 samples were successfully tested by PCR-STR. For normal individuals, thepatterns obtained by PCR-STR were two bands with 1 ： 1 area ratio or a single band. For DS cases, by contrast, the patterns revealed either three bands with area ratio of 1 ： 1 ： 1 for two STR loci, or three bands with area ratio of 1 ： 1 ： 1 for one STR loci and two bands with 2 ： 1 or 1 ： 2 area ratio for two STR loci. Based on analysis of the 7 STR markers, 14 amniotic fluid samples and 26 peripheral blood samples were regarded as DS positive. （2） For the 978 amniotic fluid samples, cytogenetie analysis was successful in 961 （98.3%）, among which 44 had an abnormal karyotype. These included 14 trisomy 21 （12 standard type, 1 mosaicism and 1 translocation）. 17 cases which failed amniocytic culture were normal upon fetal blood karyotyping. （3） Cytogenetic analysis was successful in all of the 82 peripheral blood samples, and has identified 30 （36. 6%） abnormal karyotypes, among which 26 were trisomy 21 （including 4 with translocation form）. （4） For DS positive cases, STR 1-4 showed three bands with area ratio of 1 ： 1 ： 1, or there were 2-4 loci with two bands with an area ratio of 2 ： 1 or 1 ： 2. All of the DS cases detected by PCR- STR were confirmed by karyotyping. （5） All of the 7 selected loci were informative, with their degrees of heterozygosity ranging between 0

关 键 词：聚合酶链反应 短串联重复序列 产前诊断 唐氏综合征 

分 类 号：R714.54[医药卫生—妇产科学]