Clinical Validation and Diagnostic Utility of Optical Genome Mapping in Prenatal Diagnostic Testing
Clinical Validation and Diagnostic Utility of Optical Genome Mapping in Prenatal Diagnostic Testing
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DOI：
10.1016/j.jmoldx.2023.01.006
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发表时间：
2023-03-16
影响因子：
4.1
通讯作者：
Kolhe, Ravindra
中科院分区：
文献类型：
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作者：
Sahajpal, Nikhil S.;Mondal, Ashis K.;Kolhe, Ravindra
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膜细胞或绒毛样本。然而，每种技术都有其局限性：核型分析分辨率低(>；5Mb)，FISH是目标，CMA不能检测平衡结构变异(SVS)。这些局限性要求同时或按顺序使用多项检测，以得出基因诊断结果。光学基因组作图(OGM)是一项新兴的技术，可以一次检测几种类型的SVS，但尚未在产前环境中进行评估。这项验证研究分析了我们实验室收到的114个样本，用于传统的细胞遗传学分析，包括核型分析、FISH和/或CMA。OGM法检测101条染色体异常的符合率为100%，包括29条间质/末端缺失、28条复制、26条非整倍体、6条杂合区缺失、3条三倍体基因组、4条同源染色体和1条易位，3条标记染色体和1条染色体与核型分析未确定的额外物质一致。此外，OGM在43例样本中检测到额外的临床可报告的SVS。OGM有一个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，并展示了取代目前产前诊断测试标准护理方法的潜力。
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 du-plications, 26 aneuploidies, 6 absence of heterozygosity regions, 3 triploid genomes, 4 iso-chromosomes, 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.