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Case Reports
. 2023 Mar 10:14:1121121.
doi: 10.3389/fgene.2023.1121121. eCollection 2023.

Case report: Detection of fetal trisomy 9 mosaicism by multiple genetic testing methods: Report of two cases

Na Ma  1 , Zhenhua Zhu  2 , Jiancheng Hu  1 , Jialun Pang  1 , Shuting Yang  1 , Jing Liu  1 , Jing Chen  1 , Wanglan Tang  1 , Haiyan Kuang  3 , Rong Hu  1 , Zhuo Li  4 , Hua Wang  5 , Ying Peng  1 , Hui Xi  1
Affiliations
Case Reports

Case report: Detection of fetal trisomy 9 mosaicism by multiple genetic testing methods: Report of two cases

Na Ma et al. Front Genet. .

Abstract

Chromosomal mosaicism remains a perpetual diagnostic and clinical dilemma. In the present study, we detected two prenatal trisomy 9 mosaic syndrome cases by using multiple genetic testing methods. The non-invasive prenatal testing (NIPT) results suggested trisomy 9 in two fetuses. Karyotype analysis of amniocytes showed a high level (42%-50%) of mosaicism, and chromosomal microarray analysis (CMA) of uncultured amniocytes showed no copy number variation (CNV) except for large fragment loss of heterozygosity. Ultrasound findings were unmarkable except for small for gestational age. In Case 1, further umbilical blood puncture confirmed 22.4% and 34% trisomy 9 mosaicism by CMA and fluorescent in situ hybridization (FISH) respectively. After comprehensive consideration of the genetic and ultrasound results, the two gravidas decided to receive elective termination and molecular investigations of multiple tissue samples from the aborted fetus and the placenta. The results confirmed the presence of true fetoplacental mosaicism with levels of trisomy 9 mosaicism from 76% to normal in various tissues. These two cases highlight the necessity of genetic counseling for gravidas whose NIPT results highly suggest the risk of chromosome 9 to ascertain the occurrence of mosaicism. In addition, the comprehensive use of multiple genetic techniques and biological samples is recommended for prenatal diagnosis to avoid false-negative results. It should also be noted that ultrasound results of organs with true trisomy 9 mosaicism can be free of structural abnormalities during pregnancy.

Keywords: chromosomal microarray analysis; copy number variation sequencing; karyotype; mosaicism; non-invasive prenatal testing; trisomy 9.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Results for trisomy 9 mosaicism in Case1. (A) Karyotype profiles indicating trisomy 9 (red arrows indicate the chromosome 9). (B) CMA assay results of the uncultured amniotic fluid sample for Case 1. Loss-of-heterozygosity (LOH) at 9p24.3p22.1 detected by CMA (positions of LOH are indicated by the dashed boxes). (C) FISH profiles of 22.4% trisomy 9 mosaicism in uncultured interphase umbilical blood cells using chromosome 9 centromere-specific (white) and 9qter telomeres-specific probe (red). (D) CMA assay results of uncultured umbilical blood sample for Case 1. LOH at 9p24.3p22.1 detected by CMA (positions of LOH are indicated by the dashed boxes). SmoothSignal showed 34% trisomy 9 mosaicism (x-axis: chromosomes 9; y-axis: copy number).
FIGURE 2
FIGURE 2
Results for trisomy 9 mosaicism in Case 2. (A) Karyotype profiles indicating trisomy 9 (red arrows indicated the chromosome 9). (B) FISH profiles of 8.2% trisomy 9 mosaicism in interphase uncultured oral mucosal cells using chromosome 9 centromere-specific (white) and 9qter telomeres-specific probe (red). (C) CMA assay results of uncultured amniocytes for Case 2. LOH at 9p23p13.1 and 9q33.1q34.3 detected by CMA (positions of LOH are indicated by the dashed boxes).
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