Evaluation of prenatal genetic aberrations in fetuses with gallbladder abnormalities: A retrospective cohort study

Abstract

Background With the widespread application of chromosomal microarray analysis (CMA) in prenatal diagnosis, fetal gallbladder abnormalities have been found to be associated not only with chromosomal aneuploidies but also with certain syndromes caused by submicroscopic chromosomal structural variants. This study aimed to investigate the molecular etiology of fetal gallbladder abnormalities and to provide additional evidence for clinical screening and genetic counseling regarding these anomalies. Material and methods This retrospective study included 258 fetuses diagnosed with gallbladder abnormalities through prenatal ultrasonographic screening. Among these, 167 cases underwent both karyotype analysis and CMA, 14 cases received CMA only, and 77 cases underwent karyotype analysis only. The fetuses were categorized into two groups based on the presence of additional structural anomalies: isolated gallbladder abnormalities (Group A), gallbladder abnormalities accompanied by soft markers (Group B) and gallbladder abnormalities accompanied by structural anomalies or other abnormalities (Group C). Within each of the three groups, cases were further subdivided into subgroups A1/B1/C1, A2/B2/C2, A3/B3/C3, and A4/B4/C4, corresponding to fetuses with nonvisualized gallbladder, gallbladder enlargement, small gallbladder, and other gallbladder abnormalities, respectively. Results Among the total of 258 fetuses, karyotyping identified chromosomal abnormalities in 10 cases (4.2%, 10/240), whereas SNP-array detected abnormalities in 16 cases (8.7%, 16/184). The detection rate of SNP-array was higher than that of traditional chromosome karyotype analysis, and SNP-array identified submicroscopic abnormalities in 7 additional cases that were undetectable by karyotyping. The overall detection rates were significantly higher in gallbladder abnormalities accompanied by structural anomalies or other abnormalities group than that in the isolated gallbladder abnormalities group and gallbladder anomalies accompanied by soft ultrasound markers group(P < 0.05). The highest frequency of chromosomal abnormalities was observed in fetuses presenting with both gallbladder and facial abnormalities. Conclusion For fetuses with gallbladder abnormalities, prenatal genetic diagnosis is recommended, with chromosomal microarray analysis (CMA) as the preferred testing method. It can improve the detection rate of chromosomal abnormalities associated with fetal gallbladder abnormalities and identify submicroscopic chromosomal structural variants that conventional karyotyping may miss.

The authors' abstract, as published at the source. PLoS ONE, 2026 · DOI ↗