The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China.
Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510620, China.
Genes (Basel). 2023 Sep 26;14(10):1872. doi: 10.3390/genes14101872.
(1) Purpose: Retrospective back-to-back comparisons were performed to evaluate the accuracy, effectiveness, and incremental yield of chromosome microarray analysis (CMA) and exome sequencing (ES) analysis in fetuses with digestive system malformations (DSMs). (2) Methods: In total, 595 women with fetal DSMs who underwent prenatal diagnosis were enrolled. We analyzed the diagnostic yields of CMA and ES and evaluated pregnancy outcomes. Copy number variants (CNVs) were classified according to the American College of Medical Genetics and Genomics guidelines. (3) Results: Pathogenic CNVs were detected in 11/517 (2.12%) fetuses, and variants of unknown significance (VUS) were identified in 69 (13.35%) fetuses using CMA. ES detected 29 pathogenic/likely pathogenic variants in 23/143 (16.08%) fetuses and 26/143 (18.2%) VUS. In those with other ultrasound abnormalities, the detection rate of multiple system structural malformations was 41.2%, followed by skeletal (33.3%), cardiovascular (25.4%), and central nervous system (18.6%) malformations. Of the 391 surviving children, 40 (10.2%) exhibited varying degrees of mental retardation. (4) Conclusion: A correlation exists between DSMs and chromosomal abnormalities. When combined with other systemic abnormalities, the incidence of chromosomal abnormalities increases significantly. Patients with congenital DSM are at risk of developing neurodevelopmental disorders. Combined CMA and ES detection of fetal DSM has good clinical application potential.
(1)目的：回顾性背靠背比较旨在评估染色体微阵列分析（CMA）和外显子组测序（ES）分析在消化系统畸形（DSMs）胎儿中的准确性、有效性和增量产量。(2)方法：共纳入 595 名接受产前诊断的胎儿 DSM 女性。我们分析了 CMA 和 ES 的诊断收益，并评估了妊娠结局。拷贝数变异（CNVs）根据美国医学遗传学与基因组学学院的指南进行分类。(3)结果：CMA 在 517 名胎儿中检测到 11 个致病性 CNVs，在 69 名胎儿中检测到意义不明的变异（VUS）。ES 在 23/143（16.08%）胎儿中检测到 29 个致病性/可能致病性变异，在 26/143（18.2%）胎儿中检测到 VUS。在那些伴有其他超声异常的胎儿中，多系统结构畸形的检出率为 41.2%，其次是骨骼（33.3%）、心血管（25.4%）和中枢神经系统（18.6%）畸形。在 391 名存活儿童中，40 名（10.2%）表现出不同程度的智力迟钝。(4)结论：DSMs 与染色体异常之间存在相关性。当与其他全身异常结合时，染色体异常的发生率显著增加。患有先天性 DSM 的患者有发生神经发育障碍的风险。联合 CMA 和 ES 检测胎儿 DSM 具有良好的临床应用潜力。
