Xu Yiyun, Chen Hao, Zhang Qinxin, Tan Juan, Zhou Ran, Ji Xiuqing, Luo Chunyu, Meng Lulu, Liu An, Wang Yan, Hu Ping, Xu Zhengfeng
Department of Prenatal Diagnosis, Women's Hospital of Nanjing Medical University (Nanjing Women and Children's Healthcare Hospital), Nanjing, China.
Department of Medical Genetics and Prenatal Diagnosis, Lianyungang Maternal and Child Health Hospital, Lianyungang, China.
Prenat Diagn. 2025 May;45(5):618-630. doi: 10.1002/pd.6798. Epub 2025 Apr 14.
To evaluate the clinical value of optical genome mapping (OGM) for prenatal diagnosis in fetuses with structural anomalies.
OGM was performed prospectively in 204 cases of fetuses with structural anomalies. Detection rates of OGM were investigated. Subgroup analysis was then conducted.
Overall, pathogenic or likely pathogenic (P/LP) chromosome aberrations were identified in 28 (13.7%) fetuses with structural anomalies using OGM, including 12 with numerical chromosomal abnormalities, 14 with P/LP copy number variations (CNVs) and two with balanced chromosomal rearrangements. OGM structural variation (SV) algorithm provided the structure and breakpoint information for 17 SVs and revealed six deletions, six tandem direct duplications, one inverted duplication, one paired duplication flanking a cryptic inversion and three balanced chromosomal rearrangements (one likely benign and two with breakpoints disrupting OMIM Morbid gene associated with dominant inheritance disorders). The diagnostic yields of OGM in the cystic hygroma group and multisystem malformation group were both significantly higher than those in other groups (35.7% vs. 10.3%, adjusted p = 0.018; 31.3% vs. 10.3%, adjusted p = 0.04).
Our study suggests that OGM is a reliable, comprehensive and high-resolution technology with an acceptable turnaround time that is a powerful method for prenatal diagnosis in fetuses with structural anomalies.
评估光学基因组图谱（OGM）在产前诊断结构异常胎儿中的临床价值。
对204例结构异常胎儿进行前瞻性OGM检测，研究OGM的检出率，并进行亚组分析。
总体而言，使用OGM在28例（13.7%）结构异常胎儿中鉴定出致病性或可能致病性（P/LP）染色体畸变，其中12例为染色体数目异常，14例为P/LP拷贝数变异（CNV），2例为染色体平衡重排。OGM结构变异（SV）算法为17个SV提供了结构和断点信息，发现6个缺失、6个串联直接重复、1个反向重复、1个隐匿性倒位侧翼的配对重复以及3个染色体平衡重排（1个可能为良性，2个断点破坏与显性遗传疾病相关的OMIM致病基因）。OGM在颈部水囊瘤组和多系统畸形组的诊断率均显著高于其他组（35.7%对10.3%，校正p = 0.018；31.3%对10.3%，校正p = 0.04）。
我们的研究表明，OGM是一种可靠、全面且高分辨率的技术，周转时间可接受，是产前诊断结构异常胎儿的有力方法。
