Cytogenetics Laboratory, Greenwood Genetic Center, Greenwood, South Carolina.
Department of Pathology, Medical College of Georgia, Augusta University, Augusta, Georgia.
J Mol Diagn. 2023 Apr;25(4):234-246. doi: 10.1016/j.jmoldx.2023.01.006. Epub 2023 Feb 8.
The standard-of-care diagnostic prenatal testing includes a combination of cytogenetic methods, such as karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray (CMA), using either direct or cultured amniocytes or chorionic villi sampling. However, each technology has its limitations: karyotyping has a low resolution (>5 Mb), FISH is targeted, and CMA does not detect balanced structural variations (SVs). These limitations necessitate the use of multiple tests, either simultaneously or sequentially, to reach a genetic diagnosis. Optical genome mapping (OGM) is an emerging technology that can detect several classes of SVs in a single assay, but it has not been evaluated in the prenatal setting. This validation study analyzed 114 samples that were received in our laboratory for traditional cytogenetic analysis with karyotyping, FISH, and/or CMA. OGM was 100% concordant in identifying the 101 aberrations that included 29 interstitial/terminal deletions, 28 duplications, 26 aneuploidies, 6 absence of heterozygosity regions, 3 triploid genomes, 4 isochromosomes, and 1 translocation; and the method revealed the identity of 3 marker chromosomes and 1 chromosome with additional material not determined by karyotyping. In addition, OGM detected 64 additional clinically reportable SVs in 43 samples. OGM has a standardized laboratory workflow and reporting solution that can be adopted in routine clinical laboratories and demonstrates the potential to replace the current standard-of-care methods for prenatal diagnostic testing.
标准的产前诊断检测包括细胞遗传学方法的组合，如核型分析、荧光原位杂交（FISH）和染色体微阵列（CMA），使用直接或培养的羊水细胞或绒毛取样。然而，每种技术都有其局限性：核型分析的分辨率较低（>5Mb），FISH 是靶向的，CMA 不能检测平衡结构变异（SVs）。这些局限性需要使用多种测试，无论是同时还是顺序使用，以达到遗传诊断。光学基因组图谱（OGM）是一种新兴技术，可以在单次检测中检测几种 SV 类别，但尚未在产前环境中进行评估。这项验证研究分析了 114 个样本，这些样本是在我们实验室收到的，用于传统的细胞遗传学分析，包括核型分析、FISH 和/或 CMA。OGM 在识别包括 29 个间质/末端缺失、28 个重复、26 个非整倍体、6 个杂合性缺失区域、3 个三倍体基因组、4 个等臂染色体和 1 个易位在内的 101 个异常方面的准确率为 100%；该方法还揭示了 3 个标记染色体和 1 个染色体的身份，这些染色体的额外物质无法通过核型分析确定。此外，OGM 在 43 个样本中检测到 64 个额外的具有临床报告意义的 SVs。OGM 具有标准化的实验室工作流程和报告解决方案，可以在常规临床实验室中采用，并显示出替代当前产前诊断检测标准护理方法的潜力。
