Wang Y, Cheng Q, Meng L, Luo C, Hu H, Zhang J, Cheng J, Xu T, Jiang T, Liang D, Hu P, Xu Z
State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Nanjing, China.
State Key Laboratory of Reproductive Medicine, Department of Obstetrics, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China.
Clin Genet. 2017 Jun;91(6):849-858. doi: 10.1111/cge.12926. Epub 2016 Dec 22.
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.
染色体微阵列分析（CMA）已在临床实践中常规用于儿科和产前基因诊断，但很少应用于流产分析。在本研究中，我们进行了一项前瞻性研究，以评估CMA用于孕早期流产标本基因诊断的可行性。我们使用单核苷酸多态性（SNP）阵列成功分析了551份新鲜流产标本。在这些标本中，2.9%（16/551）存在明显的母体细胞污染，被排除在研究之外。在295例（55.1%）病例中鉴定出具有临床意义的染色体异常，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/微重复以及10例（1.9%）单亲二体等（isoUPD）。15例（2.8%）获得了意义不明确的变异。值得注意的是，涉及一条单一染色体（22号染色体）的isoUPD以及两个反复出现的拷贝数变异，即22q11.2微缺失和7q11.23微缺失，被确定可能与流产有关。自然流产组中遗传畸变的频率和分布与复发性流产组无显著差异。我们的研究表明，SNP阵列是临床实践中用于流产基因诊断的一种可靠、强大且高分辨率的技术。
