[Comparison of CNV-seq and chromosomal microarray analyses of abortive tissues]

To compare the performance of copy number variation sequencing (CNV-seq) and chromosomal microarray analysis (CMA) for the analysis of abortive tissues.

Tissue samples were collected from 396 patients with missed abortion who were treated at Yancheng Maternal and Child Health Care Hospital between January 2021 and July 2024. A retrospective analysis method was employed to gather relevant clinical data of the patients. 171 samples were detected by CNV-seq combined with short tandem repeat (STR) analysis, and 225 samples were detected by CMA. Differences between the two techniques, including the detection of chromosomal aneuploidies, structural aberrations [detection of CNVs of various lengths and different CNVs types], the types of chromosomal abnormalities across different ages and gestational weeks were comprehensively compared. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2024-LS-KYLX-010).

Among the 396 samples, 256 cases were detected with chromosomal abnormalities, which yielded a detection rate of 64.6%. Among the 171 cases undergoing CNV-seq analysis, 107 (62.6%) were found with chromosomal abnormalities. Among the 225 cases undergoing CMA, 149 (66.2%) were found with chromosomal abnormalities. No significant difference was found between the two groups (Χ² = 0.566, P > 0.05). Among the autosomal number abnormalities, trisomy 16 was the most common in both groups, followed by trisomy 22, and 45,X was the most common among the abnormal number of sex chromosomes. In cases of chromosomal structural abnormalities, the CNV-seq group detected 36 CNVs, while the CMA group detected 27 CNVs. In the comparison of CNVs between the two groups based on different genome lengths, when the genome length was 100 ~ 500 kb, the CNV-seq group detected more than the CMA group, there was a statistically significant difference (Χ² = 4.974, P < 0.05). When the genome length was greater than 1 000 kb, the CMA group detected more than the CNV-seq group, there was a statistically significant difference (Χ² = 5.24, P < 0.05). Compared to different types of detected CNVs, the CMA group detected more pathogenic CNVs than the CNV-seq group, there was a statistically significant difference (Χ² = 10.176, P < 0.05), while the CNV-seq group detected more variants of uncertain significance (VUS) CNVs, there was a statistically significant difference (Χ² = 9.625, P < 0.05). The comparison of two groups based on different types of chromosomal abnormalities shows that aneuploidy was the most common in both groups. The proportion of polyploidy abnormalities was higher in the CMA group than in the CNV-seq group, there was a statistically significant difference (Χ² = 8.106, P < 0.05), and the proportion of chimerism was higher in the CNV-seq group than in the CMA group, there was a statistically significant difference (Χ² = 6.888, P < 0.05). The comparison of chromosome abnormalities distribution by age group between the CNV-seq group and the CMA group showed no statistical significance in the four age groups of ≤ 24 years, 25 ~ 29 years, 30 ~ 34 years, and ≥ 35 years (P > 0.05). Comparison of chromosomal abnormalities detected in the two groups at different gestational weeks showed that the CNV-seq group had a significantly higher detection rate for the first 8 weeks than the CMA group (Χ² = 8.419, P < 0.05), though no significant difference was found in the proportion of chromosomal abnormalities between the two groups for the 8 ~ 10 weeks, 10 ~ 12 weeks, and weeks after 12 (all P > 0.05).

CNV-seq can detect chromosomal aneuploidies, mosaicisms and more VUS. The combination of CNV-seq and STR analysis can effectively detect chromosomal polyploidy. CNV-seq requires low sample quality and genomic DNA content while achieving high success rates. In the clinics, combined CNV-seq and STR analysis can serve an effective tool for genetic diagnosis of miscarriage tissues.