Clinical application of SNP array analysis in first-trimester pregnancy loss: a prospective study
Clinical application of SNP array analysis in first-trimester pregnancy loss: a prospective study
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DOI：
10.1111/cge.12926
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发表时间：
2017-06-01
影响因子：
3.5
通讯作者：
Xu, Z.
中科院分区：
文献类型：
--
作者：
Wang, Y.;Cheng, Q.;Xu, Z.
染色体微阵列分析（CMA）已被常规应用于儿科和产前遗传学诊断的临床实践中，但很少应用于流产分析。在这项研究中，我们进行了一项前瞻性研究，以评估CMA的早期妊娠流产标本的基因诊断的可行性。我们成功地分析了551新鲜流产标本使用单核苷酸多态性（SNP）阵列。在这些标本中，2.9%（16/551）存在显著的母体细胞污染，因此从研究中排除。在295例（55.1%）病例中确定了临床显著的染色体异常，包括214例（40%）非整倍体，40例（7.5%）多倍体，19例（3.6%）部分非整倍体，12例（2.2%）致病性微缺失/微重复，10例（1.9%）单亲异二体性（isoUPD）。在15例（2.8%）中获得了不确定意义的变异。值得注意的是，isoUPD涉及一个单一的染色体（22号染色体）和两个经常性的拷贝数变异，22q11.2微缺失和7q11.23微缺失，被确定为可能与流产。自然流产组与反复流产组的遗传畸变频率和分布无显著性差异。我们的研究表明，SNP阵列是一种可靠的，强大的，高分辨率的技术，在临床实践中的基因诊断流产。
Chromosomal microarray analysis (CMA) has been used routinely in pediatric and prenatal genetic diagnosis in clinical practice, but it has rarely been applied to miscarriage analysis. In this study, we conducted a prospective study to evaluate the feasibility of CMA for genetic diagnosis of first-trimester miscarriage specimens. We successfully analyzed 551 fresh miscarriage specimens using single-nucleotide polymorphism (SNP) array. Among the specimens, 2.9% (16/551) had significant maternal cell contamination and were excluded from the study. Clinically significant chromosomal abnormalities were identified in 295 (55.1%) cases, including 214 (40%) with aneuploidy, 40 (7.5%) with polyploidy, 19 (3.6%) with partial aneuploidy, 12 (2.2%) with pathogenic microdeletion/microduplication, and 10 (1.9%) with uniparental isodisomy (isoUPD). Variants of uncertain significance were obtained in 15 cases (2.8%). Notably, isoUPD involving a single chromosome (chromosome 22) and two recurrent copy number variations, 22q11.2 microdeletion and 7q11.23 microdeletion, were identified as probably to be associated with miscarriage. The frequency and distribution of genetic aberrations in the spontaneous abortion group was not significantly different from those in the recurrent miscarriage group. Our study suggests SNP array is a reliable, robust, and high-resolution technology for genetic diagnosis of miscarriage in clinical practice.