Beschreibung:
<jats:p>Introduction: Whole-exome sequencing (WES) is becoming widely available in prenatal diagnosis. However, as with most scientific methods, WES also has its limitations. The aim of the study was to report a fetal case of RNU4ATAC-opathy which was missed by prenatal WES. Case Presentation: A 28-year-old healthy primigravida was revealed by ultrasound at 20 + 3 weeks of gestation to have a fetus with ventriculomegaly (left 15.1 mm/right 11.9 mm), hypoplastic vermis, and mild growth retardation. Chromosomal microarray analysis and trio WES failed to detect a pathogenic copy number variation and sequence variant. A repeat ultrasound at 23 + 3 weeks showed worsened growth delay and hydrocephalus (left 20.3 mm/right 11.0 mm) with vermis hypoplasia and agenesis of corpus callosum. Further study with whole-genome sequencing (WGS) detected 2 missense mutations of the noncoding RNU4ATAC (NR_023343.1) gene, n.51G>A (rs188343279) and n.16G>A (rs750325275), in the fetus, which were inherited from the father and mother, respectively. Discussion: Our study highlights the limitation of WES. WGS might be a clinical option for patients who have a structurally abnormal fetus tested negative by WES. </jats:p>