Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
Department of Clinical Genetics and Amsterdam Reproduction and Development Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Acta Obstet Gynecol Scand. 2021 Nov;100(11):2036-2043. doi: 10.1111/aogs.14256. Epub 2021 Sep 1.
The presence of an unbalanced familial translocation can be reliably assessed in the cytotrophoblast of chorionic villi. However, carriers of a balanced translocation often decline invasive testing. This study aimed to investigate whether an unbalanced translocation can also be diagnosed in cell free DNA by whole-genome non-invasive prenatal screening (NIPS).
Pregnant women carrying a fetus with an unbalanced familial translocation, for whom NIPS as well as microarray data were available, were included in this retrospective assessment. NIPS was performed in the course of the TRIDENT study.
In 12 cases, both NIPS and microarray data were available. In 10 of 12 cases the unbalanced translocation was correctly identified by NIPS without prior knowledge on parental translocation. One was missed because the fetal fraction was too low. One was missed because of technical restrictions in calling 16p gains.
This study supports the hypothesis that routine NIPS may be used for prenatal diagnosis of unbalanced inheritance of familial translocations, especially with prior knowledge of the translocation allowing focused examination of the involved chromosomal regions. Our study showed that routine shallow sequencing designed for aneuploidy detection in cell free DNA may be sufficient for higher resolution NIPS, if specialized copy number software is used and if sufficient fetal fraction is present.
在绒毛膜绒毛的滋养细胞中可以可靠地评估不平衡的家族易位的存在。然而，平衡易位的携带者通常会拒绝侵入性检测。本研究旨在探讨全基因组非侵入性产前筛查（NIPS）是否也可以在游离 DNA 中诊断不平衡易位。
本回顾性评估纳入了携带不平衡家族易位胎儿的孕妇，这些孕妇既接受了 NIPS 检测，也提供了微阵列数据。NIPS 是在 TRIDENT 研究中进行的。
在 12 例中，均提供了 NIPS 和微阵列数据。在 12 例中有 10 例通过 NIPS 正确识别了不平衡易位，而没有事先了解父母易位的情况下。有一例因胎儿比例过低而漏诊。有一例因调用 16p 增益的技术限制而漏诊。
本研究支持这样的假设，即常规 NIPS 可用于产前诊断家族易位的不平衡遗传，尤其是在事先了解易位的情况下，可对涉及的染色体区域进行有针对性的检查。我们的研究表明，如果使用专门的拷贝数软件，并且存在足够的胎儿比例，那么设计用于检测游离 DNA 中非整倍体的常规浅层测序可能足以进行更高分辨率的 NIPS。
