[Prenatal cyto- and molecular genetic analysis of low-proportion fetal chromosome mosaicisms for pregnant women with abnormal NIPT results].

OBJECTIVE

To explore the clinical phenotypes and genetic characteristics of fetuses with chromosomal abnormalities detected by non-invasive prenatal testing (NIPT) due to confined placental mosaicisms (CPM).

METHODS

A retrospective analysis was conducted on 460 fetuses with abnormal NIPT results who were admitted to Taizhou Hospital of Zhejiang Province between January 2019 and December 2024. Amniocentesis was performed to obtain amniotic fluid samples for chromosomal karyotyping analysis, copy number variation sequencing (CNV-seq), and/or interphase fluorescence in situ hybridization (FISH) assay. Short tandem repeat (STR) analysis was used to exclude maternal blood contamination. The procedures followed in this study were approved by the Medical Ethics Committee of the hospital (Ethics No.: k20201009).

RESULTS

Among the 460 fetuses with abnormal NIPT results, 456 (99.1%) had yielded consistent results by prenatal diagnosis, 4 (0.9%) were diagnosed with CPM, manifested as inconsistency between NIPT and amniotic testing results. Among these 4 cases, 3 were trisomic CPM (amniocytic karyotyping indicated trisomy 14 mosaicism mos 47,+14[2]/46[53], trisomy 18 mosaicism mos 47,+mar[96]/46[27], trisomy 21 mosaicism mos 47,+21[11]/46[40], with CNV-seq indicating normal diploid or low-proportion mosaicism); 1 had chromosome 3 microdeletion CPM (amniotic fluid karyotype showed a marker chromosome mos 47,+mar[14]/46[98], CNV-seq indicated a 3p26.3p26.2 deletion, and peripheral blood karyotyping after birth confirmed as 47,XY,+mar). Among the 4 fetuses, 3 showed no significant abnormality on ultrasound and had normal peripheral blood karyotypes after birth (46,XX or 46,XY), 1 had trisomy 18 CPM combined with ventricular septal defect and growth restriction, and the pregnancy was terminated at 23+2 weeks.

CONCLUSION

When there is inconsistency between NIPT and amniotic fluid cell karyotype analysis results, CPM should be suspected. The combined application of karyotyping analysis, CNV-seq, and FISH can effectively identify low-proportion fetal mosaicism. Combined with prenatal ultrasound monitoring, it can facilitate accurate assessment of prognosis, avoid excessive intervention, and provide important basis for prenatal genetic counseling.