Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Tianhe District, Guangzhou, 510623, China.
Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
J Assist Reprod Genet. 2022 Sep;39(9):2115-2124. doi: 10.1007/s10815-022-02527-8. Epub 2022 Jun 6.
This study aims to investigate genomic imbalance in euploid products of conceptions (POCs) detected by chromosomal microarray analysis (CMA) and its association with clinical characteristics.
In a retrospective cohort study where all women with singleton pregnancy losses underwent CMA detection of POCs, only patients with euploid POCs were included in the analysis. The clinical features were compared between those with and without a copy number variant (CNV). The pathogenic CNVs and the variant of uncertain significance (VOUS) were analyzed, and the common pathogenic CNVs and uniparental disomy (UPD) were investigated.
A total of 610 POCs were detected as chromosomal euploid, of which 176 were euploid with CNVs and 434 were euploid without CNVs. Regarding maternal age, gestational age, and history of pregnancy loss, no significant differences were found between the two groups. Furthermore, 104 pathogenic CNVs were identified in 93 POCs, and the deletion of 8p23.3 was found in 10 subjects. All CNVs greater than 3 Mb and 39.5% of CNVs ranging from 1 to 2 Mb were pathogenic, and only 3 CNVs < 1 Mb were pathogenic. UPD was detected in 12 POCs.
Besides aneuploidy, 15.24% pregnancy loss might have an association with pathogenic genomic imbalance, and the occurrence of genomic imbalance is not related to clinical characteristics. CNVs greater than 3 Mb in pregnancy losses have a high probability to be pathogenic, and approximately 40% of CNVs ranging from 1 to 2 Mb are pathogenic. The deletion of 8p23.3 is the most common pathogenic CVN in POCs of Chinese-Han women. The clinical significance of UPD in pregnancy loss needs further study.
本研究旨在探讨染色体微阵列分析（CMA）检测到的整倍体胚胎（POC）中基因组失衡及其与临床特征的关系。
在一项回顾性队列研究中，所有因单胎妊娠丢失而接受 CMA 检测的患者均纳入研究，仅对 POC 为整倍体的患者进行分析。比较了具有和不具有拷贝数变异（CNV）的患者的临床特征。分析了致病性 CNV 和意义未明的变异（VOUS），并研究了常见的致病性 CNV 和单亲二体（UPD）。
共检测到 610 个 POC 为染色体整倍体，其中 176 个 POC 为整倍体伴 CNV，434 个 POC 为整倍体不伴 CNV。两组间在母体年龄、孕龄和妊娠丢失史方面无显著差异。此外，在 93 个 POC 中鉴定出 104 个致病性 CNV，其中 10 个 POC 存在 8p23.3 缺失。所有大于 3 Mb 的 CNV 和 39.5% 的 1-2 Mb 的 CNV 为致病性，而只有 3 个小于 1 Mb 的 CNV 为致病性。在 12 个 POC 中检测到 UPD。
除了非整倍体，15.24%的妊娠丢失可能与致病性基因组失衡有关，而基因组失衡的发生与临床特征无关。妊娠丢失中大于 3 Mb 的 CNV 具有较高的致病性概率，大约 40%的 1-2 Mb 的 CNV 具有致病性。8p23.3 缺失是中国汉族女性 POC 中最常见的致病性 CVN。UPD 在妊娠丢失中的临床意义需要进一步研究。
