Department of Pathology and Cell Biology, Columbia University, New York, New York; the Departments of Statistics, Genetic Counseling, Research and Development, and Operations, Natera Inc., San Carlos, and the Reproductive Endocrinology and Infertility Division, Stanford University, Palo Alto, California.
Obstet Gynecol. 2014 Aug;124(2 Pt 1):202-209. doi: 10.1097/AOG.0000000000000325.
To report the full cohort of identifiable anomalies, regardless of known clinical significance, in a large-scale cohort of postmiscarriage products-of-conception samples analyzed using a high-resolution single-nucleotide polymorphism (SNP)-based microarray platform. High-resolution chromosomal microarray analysis allows for the identification of visible and submicroscopic cytogenomic imbalances; the specific use of SNPs permits detection of maternal cell contamination, triploidy, and uniparental disomy.
Miscarriage specimens were sent to a single laboratory for cytogenomic analysis. Chromosomal microarray analysis was performed using a SNP-based genotyping microarray platform. Results were evaluated at the cytogenetic and microscopic (greater than 10 Mb) and submicroscopic (less than 10 Mb) levels. Maternal cell contamination was assessed using information derived from fetal and maternal SNPs.
Results were obtained on 2,389 of 2,392 specimens (99.9%) that were less than 20 weeks of gestation. Maternal cell contamination was identified in 528 (22.0%) specimens. The remaining 1,861 specimens were considered to be of true fetal origin. Of these, 1,106 (59.4%) showed classical cytogenetic abnormalities: aneuploidy accounted for 945 (85.4%), triploidy for 114 (10.3%), and structural anomalies or tetraploidy for the remaining 47 (4.2%). Of the 755 (40.6%) cases considered normal at the cytogenetic level, SNP chromosomal microarray analysis revealed a clinically significant copy number change or whole-genome uniparental disomy in 12 (1.6%) and three (0.4%) cases, respectively.
Chromosomal microarray analysis of products-of-conception specimens yields a high diagnostic return. Using SNPs extends the scope of detectable genomic abnormalities and facilitates reporting "true" fetal results. This supports the use of SNP chromosomal microarray analysis for cytogenomic evaluation of miscarriage specimens when clinically indicated.
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报告在使用高分辨率单核苷酸多态性（SNP）微阵列平台分析的大规模流产产物样本队列中，无论已知临床意义如何，所有可识别的异常情况。高分辨率染色体微阵列分析可识别可见和亚微观细胞基因组不平衡；SNP 的特定使用可检测母体细胞污染、三倍体和单亲二体性。
流产标本送到一个单一的实验室进行细胞基因组分析。使用基于 SNP 的基因分型微阵列平台进行染色体微阵列分析。结果在细胞遗传和显微镜下（大于 10Mb）和亚微观（小于 10Mb）水平进行评估。使用源自胎儿和母体 SNP 的信息评估母体细胞污染。
获得了 2392 个小于 20 周妊娠的标本中的 2389 个（99.9%）的结果。在 528 个（22.0%）标本中鉴定出母体细胞污染。其余 1861 个标本被认为是真正的胎儿来源。在这些标本中，1106 个（59.4%）显示经典细胞遗传异常：非整倍体占 945 个（85.4%），三倍体占 114 个（10.3%），结构异常或四倍体占其余 47 个（4.2%）。在被认为在细胞遗传学水平正常的 755 个（40.6%）病例中，SNP 染色体微阵列分析分别在 12 个（1.6%）和 3 个（0.4%）病例中发现了临床意义上的拷贝数变化或全基因组单亲二体性。
对流产产物标本进行染色体微阵列分析可获得高诊断回报。使用 SNP 扩展了可检测基因组异常的范围，并有助于报告“真实”胎儿结果。这支持在临床需要时使用 SNP 染色体微阵列分析对流产标本进行细胞基因组评估。
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