Department of Reproductive and Genetic Diseases, Deyang People's Hospital, Deyang, Sichuan, China.
Deyang Key Laboratory of Birth Defects Prevention and Control, Deyang People's Hospital, Deyang, Sichuan, China.
Mol Genet Genomic Med. 2023 Aug;11(8):e2187. doi: 10.1002/mgg3.2187. Epub 2023 Apr 18.
Copy number variation sequencing (CNV-seq) could detect most chromosomal abnormalities except polyploidy, and quantitative fluorescence polymerase chain reaction (QF-PCR) is a supplementary method to CNV-seq in triploid detection. This study aimed to evaluate the feasibility of sequential application of CNV-seq and QF-PCR in genetic analysis of miscarriage and stillbirth.
A total of 261 fetal specimens were analyzed by CNV-seq, and QF-PCR was only further performed for samples with normal female karyotype identified by CNV-seq. Cost and turnaround time (TAT) was analyzed for sequential detection strategy. Subgroup analysis and logistic regression were carried out to evaluate the relationship between clinical characteristics (maternal age, gestational age, and number of pregnancy losses) and the occurrence of chromosomal abnormalities.
Abnormal results were obtained in 120 of 261 (45.98%) cases. Aneuploidy was the most common abnormality (37.55%), followed by triploidy (4.98%) and pathogenic copy number variations (pCNVs) (3.45%). CNV-seq could detect the triploidy with male karyotype, and QF-PCR could further identify the remaining triploidy with female karyotype. In this study, we found more male triploidies than female triploidies. With the same ability in chromosomal abnormalities detection, the cost of sequential strategy decreased by 17.35% compared with combined strategy. In subgroup analysis, significant difference was found in the frequency of total chromosomal abnormalities between early abortion group and late abortion group. Results of logistic regression showed a trend that pregnant women with advanced age, first-time abortion, and abortion earlier than 12 weeks were more likely to detect chromosomal aberrations in their products of conception.
Sequential application of CNV-seq and QF-PCR is an economic and practical strategy to identify chromosomal abnormalities in fetal tissue.
拷贝数变异测序（CNV-seq）可检测除多倍体以外的大多数染色体异常，而实时荧光定量聚合酶链反应（QF-PCR）是检测三倍体的 CNV-seq 补充方法。本研究旨在评估 CNV-seq 和 QF-PCR 序贯应用于流产和死胎遗传分析的可行性。
对 261 例胎儿标本进行 CNV-seq 分析，仅对 CNV-seq 鉴定为正常女性核型的样本进一步进行 QF-PCR。分析序贯检测策略的成本和周转时间（TAT）。进行亚组分析和逻辑回归，以评估临床特征（母亲年龄、妊娠周数和妊娠丢失次数）与染色体异常发生的关系。
261 例中有 120 例（45.98%）结果异常。非整倍体最常见（37.55%），其次是三倍体（4.98%）和致病性拷贝数变异（pCNVs）（3.45%）。CNV-seq 可检测到具有男性核型的三倍体，QF-PCR 可进一步鉴定剩余的女性核型三倍体。在本研究中，我们发现更多的男性三倍体，而不是女性三倍体。在具有相同染色体异常检测能力的情况下，序贯策略的成本比联合策略降低了 17.35%。亚组分析发现，早期流产组和晚期流产组总染色体异常频率存在显著差异。逻辑回归结果显示，高龄、首次流产、妊娠 12 周前流产的孕妇更有可能检测到其妊娠产物中的染色体异常。
CNV-seq 和 QF-PCR 的序贯应用是一种经济实用的策略，可用于鉴定胎儿组织中的染色体异常。
