The significance of trisomy 7 mosaicism in noninvasive prenatal screening

Abstract

Background This study was an evaluation of the role of noninvasive prenatal testing (NIPT) in the detection of trisomy 7 in prenatal diagnosis. Method A total of 35 consecutive cases underwent screening for trisomies by cell-free DNA testing between April 2015 and November 2017 due to suspicious NIPT results; these cases represented 0.11% of patients (35/31,250) with similar frequencies of abnormal results among the laboratories performing the tests. NIPT was offered to further screen for common fetal chromosomal abnormalities. Karyotype analysis, chromosomal microarray analysis (CMA), and next-generation sequencing (NGS) were used to detect 20, 14, and 25 patients, respectively, who accepted confirmatory diagnostic testing. Results High-risk results by NIPT were recorded for trisomy 7 alone in 29 women: dual aneuploidy in 4 patients and multiple aneuploidy in 2 patients. Karyotype analysis of amniotic fluid cells was normal in all 20 pregnancies, suggesting a probability of confined placental mosaicism. Further CMA data were obtained in 14 of the cases mentioned above, and 2 fetuses were detected with positive results with copy number variation. The NGS results suggested that all these samples were placental chimerisms of chromosome 7, except for one sample that was found to be an additional chimerism of chromosome 2, which was also consistent with the NIPT result. Conclusion Our results may be useful for the counseling of pregnant women in the detection of trisomy 7 by NIPT.

Clinical Significance of Non-Invasive Prenatal Screening for Trisomy 7: Cohort Study and Literature Review

“…Nevertheless, a placental study was not always conducted in previous expanded NIPS studies; there were very few positive cases studied and confirmed in the placenta. The study by Qi Y et al included placenta examination in 8 of 29 cases with trisomy 7 alone; this is the largest case number of placenta studies for trisomy 7 screened positive cases up to date [ 17 ]. In our study, we also examined the placenta in three (of 14) cases in cohort 1; non-mosaic trisomy 7 in the placenta was identified in one case, which was confirmed with true fetal mosaicism by AF analysis.…”

“…Interestingly, trisomy 7 identified in the CVS analysis was never confirmed by amniocentesis, suggesting the trisomic cells are most likely confined to the placenta [ 10 , 14 , 16 ]. In a recent genome-wide NIPS study by Qi Y et al, where 35 cases with positive trisomy 7 NIPS results were retrospectively reviewed [ 17 ], trisomy 7 was not confirmed in any cases who received the diagnostic testing by amniocentesis. Further investigations on 10 cases where the placenta was available indicated all these trisomy 7 NIPS-positive samples were placental mosaicism for chromosome 7 [ 17 ].…”

“…In a recent genome-wide NIPS study by Qi Y et al, where 35 cases with positive trisomy 7 NIPS results were retrospectively reviewed [ 17 ], trisomy 7 was not confirmed in any cases who received the diagnostic testing by amniocentesis. Further investigations on 10 cases where the placenta was available indicated all these trisomy 7 NIPS-positive samples were placental mosaicism for chromosome 7 [ 17 ]. However, in other studies, there was true fetal mosaicism of trisomy 7 confirmed in cases with NIPS-positive for trisomy 7, although complete clinical follow-up was still lacking [ 18 , 19 ].…”

Validation of fetal DNA fraction estimation and its application in noninvasive prenatal testing for aneuploidy detection in multiple pregnancies

“…For the T7 case, the value of was 0.24 (fetal fraction: 31.04 %). Based on other NIPT reports involving T7, it was most likely due to mosaicism. Three cases of T21 including two singletons and one twin were confirmed by karyotyping (95% CI, 29.24%‐100.00%).…”

Potential influence of parental copy number variations on noninvasive prenatal testing (NIPT): two case reports

“…In addition, a recent study reported that NIPT performed well in detecting subchromosomal microdeletions/ microduplications with a large clinical sample size through this platform [8]. Moreover, we are exploring the detection of other chromosomal abnormalities using this platform [23]. However, NIPT is a screening test, and all the abnormal results underscore the need for additional validation before routine use in practice as well as the necessity for confirmatory diagnostic testing after a positive cfDNA result.…”