Integrated cytogenetic testing resolves NIPT discordance from confined placental mosaicism
Investigators conducted a retrospective analysis of 460 fetuses with abnormal non-invasive prenatal testing results to evaluate discordance between cell-free DNA screening and amniocentesis. Only 0.9% of cases were confirmed as confined placental mosaicism, with amniotic testing revealing low-proportion trisomies or a microdeletion. Three fetuses had normal postnatal blood karyotypes and ultrasound findings, while one case with trisomy 18 mosaicism and structural anomalies led to pregnancy termination. The study demonstrates that combining karyotyping, CNV-seq, and FISH effectively identifies low-level fetal mosaicism, helping laboratories interpret NIPT discordance, refine prognostic counseling, and prevent unnecessary clinical interventions.
The original study
[Prenatal cyto- and molecular genetic analysis of low-proportion fetal chromosome mosaicisms for pregnant women with abnormal NIPT results].
- Authors
- Zhang W, Zhang W
- Journal
- Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics
- Type
- English Abstract, Journal Article
- PMID
- 42711126
Original abstract
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.