A gradual change of chromosome mosaicism from placenta to fetus leading to T18 false negative result by NIPS.

Authors:
Zhiwei Wang
Zhiwei Wang
Harvard Medical School
Israel
Xinxin Tang
Xinxin Tang
Medical College of Soochow University
China
Shuting Yang
Shuting Yang
The Key Laboratory of Conservation Biology for Endangered Wildlife of the Ministry of Education
Ting Yin
Ting Yin
School of Pharmaceutical Sciences
China
Yali Zhao
Yali Zhao
Chinese PLA General Hospital
China
Rong Zhang
Rong Zhang
Institute of Human Genetics
San Francisco | United States
Ying Gu
Ying Gu
Chinese PLA General Hospital
China

Clin Chim Acta 2019 Apr 15;495:263-268. Epub 2019 Apr 15.

Department of Prenatal Diagnosis, Lianyungang Maternal and Child Health Hospital, Lianyungang, Jiangsu 222000, China. Electronic address:

Background: Noninvasive prenatal screening (NIPS) has higher sensitivity and specificity compared to traditional prenatal screening. Nevertheless, the discordant results between the NIPS and prenatal diagnosis were occasionally reported. In current study, we investigated the genetic basis of a T18 fetus with a discordant trisomy 5 (T5) positive and trisomy 18 (T18) negative NIPS result.

Methods: NIPS was used to detect fetal DNA in maternal circulating plasma based on semiconductor sequencing platform. The aneuploidies of the fetus and different part of placental tissues were investigated by copy number variation sequencing (CNV-seq) and chromosome microarray analysis (CMA).

Results: The positive result of T5 was detected for the pregnant woman in NIPS, while T18 was found in the fetal karyotyping analysis after amniocentesis. Furthermore, placental mosaicism of T5 and T18 was found by CNV-seq and CMA, which revealed the mosaic ratio of T5 was gradually increased from umbilical cord to the placenta center, while that of T18 was gradually decreased.

Conclusion: For the reason of cell-free fetal DNA (cff DNA) in the maternal circulation originates from trophoblast cells of placenta, the level of placental mosaicism could cause false negative NIPS result in multiple aneuploidies. The present study proved that a discordant T5 positive and T18 negative NIPS result was caused by placental mosaicism. This study highlights placental mosaicism as a significant risk factor for discordant NIPS results. The result will be helpful for genetic counseling and clinical management of such pregnant woman.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cca.2019.04.064DOI Listing
April 2019
2.824 Impact Factor

Publication Analysis

Top Keywords

placental mosaicism
16
nips result
12
negative nips
12
nips
9
dna maternal
8
false negative
8
prenatal screening
8
fetal dna
8
pregnant woman
8
t18 negative
8
discordant nips
8
t18
7
mosaicism
5
result
5
placental
5
semiconductor sequencing
4
sequencing platform
4
result multiple
4
cell-free fetal
4
tissues investigated
4

Similar Publications