During 2018-2020, 94 cases of POC-NK, 38 cases of POC-CF, and 35 cases of POC-FFPE analyzed by OMA were retrieved from the laboratory’s information system [12]. For these 167 cases, the clinical indications included fetal demise (SAB, miscarriage and stillbirth) (71.2%, 119/167), suspected fetal anomaly (23.4%, 39/167), preterm premature rupture of membranes (3%, 5/167), and recurrent pregnancy loss (2.4%, 4/167); the maternal age ranged from 20 to 49 years and 46% of them were aged 35 and older. The cytogenomic abnormalities detected from OMA on POC-NK, POC-CF and POC-FFPE are summarized in Table 1.
Table 1 Cytogenomic abnormalities in POC-NK, CF and FFPE
|
Abnormalities
|
POC-NK
|
POC-CF
|
POC-FFPE
|
|
n=94
|
n=38
|
n=35
|
Chr Abn. (ADR)
|
1 (1%)
|
9 (23%)
|
19 (54%)
|
Aneuploidies
|
|
|
|
Trisomy 4
|
|
1
|
|
Trisomy 6
|
|
|
1
|
Trisomy 8
|
|
|
1
|
Trisomy 9
|
|
|
3
|
Trisomy 12
|
|
|
1
|
Trisomy 13
|
1
|
|
1
|
Trisomy 14
|
|
|
1
|
Trisomy 15
|
|
1
|
1
|
Trisomy 16
|
|
|
3
|
Trisomy 20
|
|
|
1
|
Trisomy 21
|
|
2
|
|
Trisomy 22
|
|
1
|
|
Monosomy X
|
|
|
2
|
Monosomy 21
|
|
|
2
|
Triploidies
|
|
|
|
69,XXX
|
|
2
|
1
|
69,XXY
|
|
2
|
|
70,XXX,+21
|
|
|
1
|
pCNV (ADR)
|
1 (1%)
|
1 (3%)
|
1 (3%)
|
del(X)(p22.33p22.31)
|
|
1
|
|
del(18)(q23)
|
|
|
1
|
del(22)(q11.21)
|
1
|
|
|
Total Abn Cases (ADR)
|
2 (2%)
|
10 (26%)
|
20 (57%)
|
Of the 94 POC-NK cases, 43 cases were male and 51 cases were female. Two cases (2%, 2/94) were detected with an abnormal result. One case was detected with a normal female karyotype from cultured villi cells. Re-evaluation by OMA using DNA from FFPE showed a male sex pattern and three copies of chromosome 13. These findings indicated a false negative result from karyotyping of cultured maternal cells. Another case with a normal female karyotype was detected with a 2.586 Mb deletion at 22q11.21 (chr22:18876425_21462601x1) by OMA and confirmed by FISH. This deletion includes the TBX1 gene and is diagnostic for DiGeorge/velocardiofacial syndrome. Region of homozygosity (ROH) in about 3% of genome was detected in two cases. OMA was also performed on four cases with unbalanced or balanced chromosomal rearrangements (Table 2). In one case with a trisomy 13 and a derivative chromosome 4 from a 4q32.1/9q34.2 translocation of paternal origin, OMA result confirmed trisomy 13, a 33.540 Mb deletion of 4q32.1q35.2, a 4.916 Mb duplication of 9q34.2q34.3, and also absence of genes at breakpoints 4q32.1 and 9q34.2. In another case with a mosaic pattern of an isodicentric chromosome 8, OMA confirmed a 33.090 Mb deletion of 8p23.3p12, a 113.1 Mb duplication of 8p12q24.3, and likely an interruption of the FUT10 gene at the fusion point. Further parental chromosome analyses showed normal result; thus, this idic(8) in the fetus was de novo. Figure 1 shows the karyotype and OMA results for these two cases. Two cases with a balanced translocation had a normal result by OMA, indicating an absence of cryptic imbalance in this translocation.
Table 2 OMA results on four cases with balanced/unbalanced chromosomal rearrangements
|
Kayotypes
|
OMA results (GRCh37/hg19)
|
|
47,XX,der(4)t(4;9)(q32.1;q34.2)pat,+13
|
arr 4q32.1q35.2(157375250_190915650)x1, 9q34.2q34.3(136859048_141054761)x3,(13)x3
|
|
mos 46,XX,idic(8)(p12)dn[9]/46,XX[11]
|
arr 8p23.3p12(172416_33262869)x1, 8p12q24.3(33262870_146363022)x3
|
|
46,XY,t(1;10)(p32;q11.2)
|
Normal
|
|
46,XY,t(1;12)(q32;q24.1)
|
Normal
|
|
MA: maternal age
|
|
Of the 38 cases of POC-CF, 16 cases were male and 22 were female, and 10 cases (26%, 10/38) were detected with an abnormal result. The abnormal findings included a triploidy in four cases, trisomy 21 in two cases, trisomy 4 and 15 each in one case, trisomy 22 with a deletion of 21p11.2q11.2 in one case, and a 7.614 Mb deletion of Xp22.33p22.31 (chrX:177941_7792383x0) in a male case. The case of trisomy 22 with a deletion of 21p and proximal region of 21q likely resulted from a 21q/22p translocation. The couple experienced unexplained recurrent pregnancy loss, and chromosome analysis found normal results. Of the ten abnormal cases in POC-CF, aneuploidies, triploidies and pCNV accounted for 50% (5/10), 40% (4/10) and 10% (1/10), respectively.
Of the 35 cases of POC-FFPE, 14 cases were male and 21 were female, and 20 cases (57%, 20/35) were detected with an abnormal result. The abnormal findings included a triploidy in two cases, monosomy X in two cases, trisomy 16 in three cases, trisomy 9 in three cases, monosomy 21 in two cases, trisomies 6, 8, 12, 13, 14, 15 and 20 each in one case, and a 2.975 Mb deletion at 18q23 (chr18:75032971_78007784x1) in one case. MCC was noted in one case with a normal female pattern and multiple BAF in OMA. Of the 20 abnormal cases in POC-FFPE, aneuploidies, triploidies and pCNV accounted for 85% (17/20), 15% (2/20) and 5% (1/20), respectively.