Diderich Karin E M, Klapwijk Jasmijn E, van der Schoot Vyne, Brüggenwirth Hennie T, Joosten Marieke, Srebniak Malgorzata I
Department of Clinical Genetics, Erasmus MC, Rotterdam, the Netherlands.
Appl Clin Genet. 2023 May 15;16:89-97. doi: 10.2147/TACG.S411185. eCollection 2023.
The yield of genetic prenatal diagnosis has been notably improved by introducing whole genome chromosomal microarray (CMA) and prenatal exome sequencing (pES). However, together with increased numbers of diagnoses made, the need to manage challenging findings such as variants of unknown significance (VUS) and incidental findings (IF) also increased. We have summarized the current guidelines and recommendations and we have shown current solutions used in our tertiary center in the Netherlands. We discuss four of the most common clinical situations: fetus with normal pES results, fetus with a pathogenic finding explaining the fetal phenotype, fetus with a variant of uncertain clinical significance fitting the phenotype and fetus with a variant leading to an incidental diagnosis. Additionally, we reflect on solutions in order to facilitate genetic counseling in an NGS-era.
通过引入全基因组染色体微阵列（CMA）和产前外显子组测序（pES），遗传性产前诊断的检出率得到了显著提高。然而，随着诊断数量的增加，处理诸如意义未明的变异（VUS）和偶发发现（IF）等具有挑战性的结果的需求也增加了。我们总结了当前的指南和建议，并展示了我们荷兰三级中心目前使用的解决方案。我们讨论了四种最常见的临床情况：pES结果正常的胎儿、有致病性发现可解释胎儿表型的胎儿、有符合表型但临床意义不确定的变异的胎儿以及有导致偶发诊断的变异的胎儿。此外，我们思考了一些解决方案，以便在二代测序时代促进遗传咨询。
