PMC10036773_01
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).
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F1
Genetic amniocentesis test revealed a karyotype of mos 47,XX,+9 [25]/46,XX [25], indicating a level of 50% trisomy 9 mosaicism (Figure 1A). United States) revealed an 18.54 Mb loss of heterozygosity at 9p24.3p22.1, arr [GRCh37] 9p24.3p22.1 (216,123_18,758,836) x 2 hmz (Figure 1B). As there was no copy number variation (CNV) in the CMA results, and the prenatal ultrasound findings at 23+3 weeks of gestation were unremarkable, further invasive prenatal diagnosis by percutaneous umbilical blood sampling was performed at 27 weeks of gestation to confirm the trisomy 9 mosaicism. Karyotype analysis of umbilical blood identified only 1 cell with an abnormal 47,XX,+9 karyotype among 100 metaphase cells. According to the International System for Human Cytogenomic Nomenclature guidelines and recommendations, this karyotype should be normally reported as 46,XX. Interphase fluorescent in situ hybridization (FISH) analysis on uncultured fetal cord blood showed 22.4% (35/156) trisomy 9 mosaicism (Figure 1C). CMA analysis on the DNA extracted from uncultured umbilical blood detected a gene dosage increase of chromosome 9 and loss of heterozygosity for a large fragment of chromosome 9: arr [GRCh37] 9p24.3q34.3 (208,454_141,018,648) x 3 [0.34]; arr [GRCh37] 9p24.3p22.1 (216,123_18,782,021) x 2 hmz (Figure 1D). Ultrasound findings at 28+4 weeks of gestation showed no structural abnormalities except for those slightly smaller than the gestational age, with a biparietal diameter of 7.8 cm (97.5th), a head circumference of 26.1 cm (14.7th), an abdominal circumference of 21.8 cm (2nd), a humerus length of 4.7 cm (14.7th), a femur length of 5.2 cm (14.7th), and a fetal weight assessment of 1040 g (5.5th). The levels of trisomy 9 mosaicism were 6% in the DNA of uncultured amniocytes following CMA testing, 23% in uncultured umbilical blood, and 21% in the umbilical cord (Supplementary Figure S1).
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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F2
Genetic amniocentesis analysis revealed the existence of trisomy 9 mosaicism, mos 47,XY,+9 [21]/46,XY [29] with a 42% level of trisomy 9 mosaicism (Figure 2A). CMA of uncultured amniocytes with the Affymetrix CytoScan 750 K Array showed no CNV on chromosome 9 except for 24.96 Mb and 19.22 Mb loss of heterozygosity at 9p23p13.1 and 9q33.1q34.3: arr [GRCh37] 9p23p13.1 (13,814,169_38,771,831) x 2 hmz and arr [GRCh37] 9q33.1q34.3 (121,790,571_141,011,581) x 2 hmz (Figure 2B). FISH analysis of uncultured oral mucosal cells with chromosome 9p-ter and 9q-ter FISH probes detected trisomy 9 in 16 (8.2%) of 196 cells examined (Figure 2C).
PMC10036773_02
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).
fgene-14-1121121-g002.jpg
PMC10036773_02_fgene-14-1121121-g002.jpg
F2
Genetic amniocentesis analysis revealed the existence of trisomy 9 mosaicism, mos 47,XY,+9 [21]/46,XY [29] with a 42% level of trisomy 9 mosaicism (Figure 2A). CMA of uncultured amniocytes with the Affymetrix CytoScan 750 K Array showed no CNV on chromosome 9 except for 24.96 Mb and 19.22 Mb loss of heterozygosity at 9p23p13.1 and 9q33.1q34.3: arr [GRCh37] 9p23p13.1 (13,814,169_38,771,831) x 2 hmz and arr [GRCh37] 9q33.1q34.3 (121,790,571_141,011,581) x 2 hmz (Figure 2B). FISH analysis of uncultured oral mucosal cells with chromosome 9p-ter and 9q-ter FISH probes detected trisomy 9 in 16 (8.2%) of 196 cells examined (Figure 2C).