背景:染色体畸变是出生缺陷的最重要病因。光学基因组作图是一种新颖的细胞遗传学工具,用于在单个测定中检测广泛的染色体畸变。但是光学基因组图谱在产前诊断中的相关临床可行性研究是有限的。
方法:我们对34例胎儿的羊水样本进行了光学基因组图谱分析,这些胎儿具有各种临床适应症和通过标准护理技术检测到的染色体畸变,包括核型分析,荧光原位杂交,和/或染色体微阵列分析。
结果:总计,我们分析了34份羊水样本的46个染色体畸变,包括5个非整倍体,10个大拷贝数变化,27个微缺失/微重复,2易位,1个同位染色体,和1个区域的纯合性。总的来说,我们的定制分析策略可以证实45个染色体畸变。光学基因组作图以盲目的方式使用标准的护理方法对所有染色体畸变进行了97.8%的一致临床诊断。与广泛使用的染色体微阵列分析相比,光学基因组作图还确定了7例重复或三次重复的重复片段的相对方向和位置。光学基因组作图提供的额外信息将有助于表征复杂的染色体重排,并使我们能够提出解释重排和预测遗传复发风险的机制。
结论:我们的研究强调,光学基因组作图可以在单个测试中提供有关染色体畸变的全面而准确的信息,这表明光学基因组作图有可能成为产前诊断的有前途的细胞遗传学工具。
Chromosomal aberrations are the most important etiological factors for birth defects. Optical genome mapping is a novel cytogenetic tool for detecting a broad range of chromosomal aberrations in a single assay, but relevant clinical feasibility studies of optical genome mapping in prenatal diagnosis are limited.
We retrospectively performed optical genome mapping analysis of amniotic fluid samples from 34 fetuses with various clinical indications and chromosomal aberrations detected through standard-of-care technologies, including karyotyping, fluorescence in situ hybridization, and/or chromosomal microarray analysis.
In total, we analyzed 46 chromosomal aberrations from 34 amniotic fluid samples, including 5 aneuploidies, 10 large copy number variations, 27 microdeletions/microduplications, 2 translocations, 1 isochromosome, and 1 region of homozygosity. Overall, 45 chromosomal aberrations could be confirmed by our customized analysis strategy. Optical genome mapping reached 97.8% concordant clinical diagnosis with standard-of-care methods for all chromosomal aberrations in a blinded fashion. Compared with the widely used chromosomal microarray analysis, optical genome mapping additionally determined the relative orientation and position of repetitive segments for seven cases with duplications or triplications. The additional information provided by optical genome mapping will be conducive to characterizing complex chromosomal rearrangements and allowing us to propose mechanisms to explain rearrangements and predict the genetic recurrence risk.
Our study highlights that optical genome mapping can provide comprehensive and accurate information on chromosomal aberrations in a single test, suggesting that optical genome mapping has the potential to become a promising cytogenetic tool for prenatal diagnosis.