Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, VIC, Australia.
Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia.
Genet Med. 2020 Dec;22(12):1944-1955. doi: 10.1038/s41436-020-0930-2. Epub 2020 Aug 18.
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.
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.
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.
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.
平衡易位携带者产生易位不平衡配子的风险增加，导致流产、胎儿畸形和出生缺陷。我们试图确定全基因组游离胎儿 DNA 无创产前筛查（gw-NIPS）是否可以替代这些染色体重排携带者的产前诊断。
这一系列病例为回顾性分析，纳入了 42 例单胎妊娠，其中 1 名父母携带平衡易位。gw-NIPS 于 2015 年 8 月至 2018 年 3 月进行。纳入标准为至少有一个易位片段≥15Mb。
40 个样本（95%）获得了有意义的结果；7 例（17.5%）为易位不平衡的高风险，并经诊断性检测证实。其余 33 个有意义的样本为低风险，经诊断性检测或新生儿正常体格检查证实。该试验系列的检测敏感性为 100%（95%置信区间：64.6-100%），特异性为 100%（95%置信区间：89.6-100%）。
我们证明 gw-NIPS 是大多数易位携带者的潜在选择。这种方法的进一步确认可能会导致这种非侵入性替代方法的采用。
