Purpose

Of 86,902 prenatal genome-wide cell-free DNA (cfDNA) screening tests, 4,121 were positive for a chromosome abnormality. This study examines 490 cases screen-positive for one or more subchromosomal copy-number variants (CNV) from genome-wide cfDNA screening.

Methods

Cases positive for one or more subchromosomal CNV from genome-wide cfDNA screening and diagnostic outcomes were compiled. Diagnostic testing trends were analyzed, positive predictive values (PPVs) were calculated, and the type of chromosomal abnormalities ultimately confirmed by diagnostic testing were described.

Results

CNVs were identified in 0.56% of screened specimens. Of the 490 cases screen-positive for one or more CNV, diagnostic outcomes were available for 244 cases (50%). The overall PPV among the cases with diagnostic outcomes was 74.2% (95% CI: 68.1–79.5%) and 71.8% (95% CI: 65.5–77.4%) for “fetal-only” events. Overall, isolated CNVs showed a lower PPV of 61.0% (95% CI: 52.5–68.8%) compared to complex CNVs at 93.9% (95% CI: 86.6–97.5%). Isolated deletions/duplications and unbalanced structural rearrangements were the most common diagnostic outcomes when isolated and complex CNVs were identified by cfDNA screening, respectively.

Conclusion

Genome-wide cfDNA screening identifies chromosomal abnormalities beyond the scope of traditional cfDNA screening, and the overall PPV associated with subchromosomal CNVs in cases with diagnostic outcomes was >70%.

中文翻译：

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全基因组无细胞 DNA 筛选：关注拷贝数变异

目的

在 86,902 项产前全基因组游离 DNA (cfDNA) 筛查测试中，4,121 项染色体异常呈阳性。本研究检查了来自全基因组 cfDNA 筛查的 490 例筛查阳性的一个或多个亚染色体拷贝数变异 (CNV) 病例。

方法

对来自全基因组 cfDNA 筛查和诊断结果的一种或多种亚染色体 CNV 呈阳性的病例进行了汇总。分析诊断检测趋势，计算阳性预测值 (PPV)，并描述最终通过诊断检测确认的染色体异常类型。

结果

在 0.56% 的筛选标本中发现了 CNV。在一项或多项 CNV 筛查阳性的 490 例病例中，244 例 (50%) 可获得诊断结果。具有诊断结果的病例中的总体 PPV 为 74.2%（95% CI：68.1-79.5%）和“仅胎儿”事件的 71.8%（95% CI：65.5-77.4%）。总体而言，分离的 CNV 的 PPV 较低，为 61.0%（95% CI：52.5-68.8%），而复杂的 CNV 为 93.9%（95% CI：86.6-97.5%）。当通过 cfDNA 筛选分别鉴定出孤立的和复杂的 CNV 时，孤立的缺失/重复和不平衡的结构重排是最常见的诊断结果。

结论

全基因组 cfDNA 筛查可识别超出传统 cfDNA 筛查范围的染色体异常，在具有诊断结果的病例中，与亚染色体 CNV 相关的总体 PPV 大于 70%。