Cytogenetic and molecular genetic analysis of three fetuses at high risk of trisomy-16 detected by cell-free fetal DNA testing
10.3760/cma.j.cn113903-20200812-00791
- VernacularTitle:三例胎儿游离DNA检测提示16-三体高风险孕妇的产前细胞和分子遗传学分析
- Author:
Na MA
1
;
Zhengjun JIA
;
Wanglan TANG
;
Jing LIU
;
Hui XI
;
Ying PENG
;
Jiancheng HU
;
Shuting YANG
;
Rong HU
;
Hua WANG
;
Jing CHEN
Author Information
1. 湖南省妇幼保健院医学遗传科，长沙 410008
- Keywords:
Trisomy;
Chromosomes;
Noninvasive prenatal testing;
Mosaicism;
Placenta;
Genomic sequencing
- From:
Chinese Journal of Perinatal Medicine
2021;24(8):608-613
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the power and prenatal diagnosis strategies of cell-free fetal DNA (cffDNA) testing for chromosomal aneuploidy screening apart from trisomy-13/18/21.Methods:This study collected the clinical data of three cases at high risk of trisomy-16 indicated by cffDNA testing in Hunan Provincial Maternal and Child Health Care Hospital from March 2019 to March 2020. Results of the conventional G-banding karyotype analysis of amniotic fluid, single nucleotide polymorphism array (SNP-array) and low-coverage massively parallel copy number variation sequencing (CNV-seq) of placenta/fetal skin samples were analyzed.Results:(1) cffDNA testing results suggested that case 1-3 were at high risk of trisomy-16 and the Z values of chromosome 16 were 20.57, 24.88 and 17.87, respectively. (2) Karyotype analysis of amniotic fluid samples did not identify any abnormalities in Case 1 and 2, while SNP-array revealed a 19.2 Mb and 23.0 Mb heterozygous deletion at 16p13.3p12.3 and 16q22.1q24.3 in Case 1, and a 16.0 Mb loss of heterozygosity at 16q22.3q24.3 in Case 2. Case 3 had a mosaicism karyotype of 47,XY,+16[3]/46,XY[97] and SNP-array analysis showed no heterozygous deletion greater than 5 Mb or copy number variation. (3) Ultrasonography indicated fetal growth restriction in Case 1 and 2 and fetal death in Case 3. All three pregnancies were terminated. CNV-seq analysis of placental tissue in the center of both fetal and maternal side revealed mosaic trisomy 16, with the copy numbers of chromosome 16 of 2.56/2.70, 2.73/2.82, 2.80/2.81, respectively. However, no copy number variation was detected in Case 1 or 2 by CNV-seq analysis of fetal skin tissues. Conclusions:cffDNA testing has a certain power in detecting trisomy-16 apart from trisomy-13/18/21. For high-risk cases of trisomy-16 indicated by cffDNA testing, SNP-array analysis combined with karyotype analysis is suggested to rule out low-level mosaicism and loss of heterozygosity.
