染色体微阵列芯片联合核型分析用于产前诊断价值

Value of chromosome microarray technique combined with karyotype analysis for prenatal diagnosis

目的:探讨染色体微阵列芯片(CMA)与核型分析对各类异常胎儿产前遗传学诊断价值。方法:以本院2019年1—12月行侵入性产前诊断且遗传学结果异常的80例孕妇作为研究对象,诊断指征主要包括超声结构畸形、软指标异常、血清学筛查高风险、神经管畸形(NIPT)筛查高风险、高龄孕妇等,均同时行核型分析和CMA检测,分析两种方法对各类高危胎儿的检出率及差异性。结果:在超声结构及软指标异常27例中,核型和CMA分别检出了11例和24例阳性样本,其中20例结果不完全吻合,在核型正常样本中CMA额外检出15例微缺失/微重复,而在CMA正常样本中核型额外检出1例多态性(46,XN,1qh+)和2例染色体结构变异(45,XN,der(13;14)(q10;q10)、46,XN,inv(9)(p12q13));在22例不良孕产史家系中,CMA额外检出15例亚显微结构畸变(22q11.21微缺失综合征、16p11.2微缺失综合征、Xp22.31微缺失等)、杂合性缺失/单亲二倍体(LOH/UPD)等,核型额外发现4例多态性;此外,核型和CMA在高龄孕妇、血清学筛查高风险、NIPT筛查高风险、夫妻一方表型/染色体异常或近亲婚配等高风险样本中也联合检出平衡性畸变、亚显微拷贝数变异、LOH/UPD、嵌合体等畸变;结论:对于不同产前诊断高风险指征孕妇,核型分析和CMA联合应用,可高效检出平衡性畸变、微缺失/微重复、LOH/UPD、低比例嵌合体等,为胎儿预后评估及夫妻再生育提供科学依据。

Objective:To investigate the value of chromosome microarray(CMA)technique combined with karyotype analysis for prenatal genetic diagnosis of fetuses with various abnormalities.Methods:80 pregnant women who underwent invasive prenatal diagnosis and had abnormal genetic results were selected as the research subjects from January to December 2019.The diagnostic indications mainly included the structural abnormalities and abnormal soft indicators by ultrasound,and the screening high-risk,the no-invasive prenatal screening(NIPT)positive,the pregnant women with advanced age,etc.Both karyotyping and CMA testing were all given to these women during the same gestational weeks,and the detection rates and differences of various high-risk situation of the fetuses of the women by which were analyzed.Results:Among the 27 women with abnormal fetal structure and soft index by ultrasound,the positive women were detected by karyotype and CMA were 11 cases and 24 cases,respectively,and 20 women had no completely consistent of results by karyotype and CMA.In the women with normal results by karyotype,15 women had microdeletion/microduplication of chromosome were detected by CMA additionally.In the women with normal results by CMA,1 case with polymorphism of chromosome(46,XN,1 qh+)and 2 cases with chromosomal structural variations(45,XN,der(13;14)(q10;Q10),and 46,XN,inv(9)(p12 q13))were found by karyotype analysis additionally.In 22 women with the histories of abnormal pregnancy,15 women with submicrostructural aberrations(22 q11.21 microdeletion syndrome,16 p11.2 microdeletion syndrome,Xp22.31 microdeletion syndrome,etc.),and with the heterozygotic deletion/uniparental diploid(LOH/UPD)were detected by CMA additionally,and 4 cases with polymorphism of chromosome by CMA.In addition,karyotype combined with CMA also could detect the balance aberrations,submicroscopic copy number variation,LOH/UPD,and chimerism,and other abnormal chromosome of the pregnant women with advanced age,with serological screening high-risk situation,with NIPT screening high-risk situation,with phenotypic/chromosomal abnormalities of one spouse,or with inbreeding high-risk situation.Conclusion:Karyotype analysis combined with CMA used in the pregnant women with different prenatal diagnosis indications can efficiently detect their balance aberrations,micro-deletion/micro-duplication,LOH/UPD,low-proportion mosaicism,etc.,which can provide scientific evidences for evaluating the prognosis of their fetus and their reproduction.