Purpose

Balanced reciprocal translocation carriers are at increased risk of producing gametes with unbalanced forms of the translocation leading to miscarriage, fetal anomalies, and birth defects. We sought to determine if genome-wide cell-free DNA based noninvasive prenatal screening (gw-NIPS) could provide an alternative to prenatal diagnosis for carriers of these chromosomal rearrangements.

Methods

This pilot series comprises a retrospective analysis of gw-NIPS and clinical outcome data from 42 singleton pregnancies where one parent carried a balanced reciprocal translocation. Gw-NIPS was performed between August 2015 and March 2018. Inclusion criteria required at least one translocation segment to be ≥15 Mb in size.

Results

Forty samples (95%) returned an informative result; 7 pregnancies (17.5%) were high risk for an unbalanced translocation and confirmed after diagnostic testing. The remaining 33 informative samples were low risk and confirmed after diagnostic testing or normal newborn physical exam. Test sensitivity of 100% (95% confidence interval [CI]: 64.6–100%) and specificity of 100% (95% CI: 89.6–100%) were observed for this pilot series.

Conclusion

We demonstrate that gw-NIPS is a potential option for a majority of reciprocal translocation carriers. Further confirmation of this methodology could lead to adoption of this noninvasive alternative.

中文翻译：

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平衡相互易位携带者的全基因组无创产前筛查。

目的

平衡相互易位携带者产生具有不平衡易位形式的配子的风险增加，导致流产、胎儿异常和出生缺陷。我们试图确定基于全基因组无细胞 DNA 的无创产前筛查 (gw-NIPS) 是否可以为这些染色体重排的携带者提供产前诊断的替代方法。

方法

该试点系列包括对 42 例单胎妊娠的 gw-NIPS 和临床结果数据的回顾性分析，其中一位父母进行了平衡的相互易位。Gw-NIPS 在 2015 年 8 月至 2018 年 3 月期间进行。纳入标准要求至少一个易位片段的大小≥15 Mb。

结果

四十个样本（95%）返回了一个信息丰富的结果；7 次怀孕 (17.5%) 存在不平衡易位的高风险，并在诊断测试后确认。其余 33 个信息样本为低风险，并在诊断测试或正常新生儿体检后确认。该试验系列观察到 100%（95% 置信区间 [CI]：64.6–100%）的测试灵敏度和 100%（95% CI：89.6–100%）的特异性。

结论

我们证明 gw-NIPS 是大多数相互易位携带者的潜在选择。对这种方法的进一步确认可能会导致采用这种非侵入性替代方法。