Population characteristics
A total of 5289 patients (4871 adults (> 14 years) and 418 children (≤ 14 years)) performed karyotype analysis were recruited in the study, and the age ranges from 1 day to 67 years old. In addition, karyotype analysis was performed on 2882 fetuses, including 382 villi samples, 2372 amniotic fluid samples and 128 umbilical cord blood samples.
Chromosomal abnormalities of peripheral blood samples
Chromosomal abnormalities were detected in a total of 392 peripheral blood samples, and the abnormality detection rate (ADR) was 7.41% (392/5,289), which 6.73% (328/4,871) in adults and 15.31% (64/418) in children. The ADR for sex chromosome aneuploidies, autosomal aneuploidies, structural abnormalities and chromosome polymorphisms were 1.29% (68/5,289), 0.72% (38/5,289), 1.55% (82/5,289) and 3.86% (204/5,289) for all peripheral blood samples, which 1.21% (59/5,289), 0.12% (6/5,289), 1.50% (73/5,289), 3.90% (190/5,289) for adults and 2.15% (9/418), 7.65% (32/418), 2.15% (9/418), 3.35% (14/418) for children. The ADR of chromosome numerical abnormalities in children cases was significantly higher than those in adults (10.05% vs. 1.33%, P < 0.05) (Table 1).
Table 1
Chromosomal abnormalities detected in adults and children.
Chromosomal abnormalities
|
Adults (n=4871)
|
Children (n=418)
|
Total (n=5289)
|
No. Abn Cases
|
ADR (%)
|
RF (%)
|
No. Abn Cases
|
ADR (%)
|
RF (%)
|
No. Abn Cases
|
ADR (%)
|
RF (%)
|
Numerical abnormality
Sex Chromosome Aneuploidy
|
|
|
|
|
|
|
|
|
|
Males
|
|
|
|
|
|
|
|
|
|
47,XXY
|
46
|
0.94
|
14.07
|
1
|
0.24
|
1.56
|
47
|
0.89
|
11.99
|
45,X[22]/46,X,Yqh-[28]
|
1
|
0.02
|
0.30
|
0
|
0.00
|
0.00
|
1
|
0.02
|
0.26
|
45,XO[37]/46,XY[13]
|
1
|
0.02
|
0.30
|
0
|
0.00
|
0.00
|
1
|
0.02
|
0.26
|
46,XY[36]/47,XXY[64]
|
1
|
0.02
|
0.30
|
0
|
0.00
|
0.00
|
1
|
0.02
|
0.26
|
47,XYY
|
0
|
0.00
|
0.00
|
0
|
0.00
|
0.00
|
0
|
0.00
|
0.00
|
48,XXYY
|
0
|
0.00
|
0.00
|
1
|
0.24
|
1.56
|
1
|
0.02
|
0.26
|
48,XXXY
|
0
|
0.00
|
0.00
|
0
|
0.00
|
0.00
|
0
|
0.00
|
0.00
|
Females
|
|
|
|
|
|
|
|
|
|
45,XO
|
6
|
0.14
|
1.83
|
6
|
1.44
|
9.38
|
12
|
0.23
|
3.06
|
47,XXX
|
2
|
0.04
|
0.61
|
0
|
0.00
|
0.00
|
2
|
0.04
|
0.51
|
45,X[10]/46,XX[40]
|
1
|
0.02
|
0.30
|
0
|
0.00
|
0.00
|
1
|
0.02
|
0.26
|
46,XX[45]/47,XXX[5]
|
1
|
0.02
|
0.30
|
0
|
0.00
|
0.00
|
1
|
0.02
|
0.26
|
45,X[62]/46,X,der(X)(p11.2)[38]
|
0
|
0.00
|
0.00
|
1
|
0.24
|
1.56
|
1
|
0.02
|
0.26
|
Subtotal
|
59
|
1.21
|
17.99
|
9
|
2.15
|
14.06
|
68
|
1.29
|
17.35
|
Autosomal Aneuploidy
|
|
|
|
|
|
|
|
|
|
Trisomy 21
|
6
|
0.12
|
1.83
|
32
|
7.65
|
50.00
|
38
|
0.72
|
9.69
|
Trisomy 18
|
0
|
0.00
|
0.00
|
0
|
0.00
|
0.00
|
0
|
0.00
|
0.00
|
Trisomy 13
|
0
|
0.00
|
0.00
|
0
|
0.00
|
0.00
|
0
|
0.00
|
0.00
|
Subtotal
|
6
|
0.12
|
1.83
|
32
|
7.65
|
50.00
|
38
|
0.72
|
9.69
|
Total
|
65
|
1.33
|
19.82
|
41
|
9.81
|
64.06
|
106
|
2.00
|
27.04
|
Structural abnormality
|
73
|
1.50
|
22.26
|
9
|
2.15
|
14.06
|
82
|
1.55
|
20.92
|
Chromosome polymorphism
|
190
|
3.90
|
57.93
|
14
|
3.35
|
21.88
|
204
|
3.86
|
52.04
|
All chromosomal abnormalities
|
328
|
6.73
|
100.00
|
64
|
15.31
|
100.00
|
392
|
7.41
|
100.00
|
ADR, abnormality detection rate (%); RF, relative frequency by (%); *Statistically different from ADR in prenatal setting (P< 0.05).
Among cases with chromosomal abnormalities, numerical abnormalities, chromosomal structural abnormalities and chromosome polymorphism accounted for 27.04% (106/392), 20.92% (82/392) and 52.04% (204/392), respectively. The most frequently seen numerical chromosomal abnormalities by relative frequency (RF) were 47,XXY, trisomy 21, and 45,XO at 11.99%, 9.69%, and 3.06%. In adults, the most frequently seen numerical chromosomal abnormalities by RF were 47,XXY, trisomy 21, and 45,XO at 14.07%, 1.83%, and 1.83%. In children, the most frequently seen numerical chromosomal abnormalities by RF were trisomy 21, and 45,XO at 50.0%, and 9.38% (Table 1).
The most common structural chromosomal abnormalities were 46,XN,dup(1)(q11q12) (n = 11; RF = 13.41%), followed by 46,X,inv(Y)(p11.2q11.23) (n = 10; RF = 12.20%), and 45,XY,der(13;14)(q10;q10) (n = 5; RF = 6.10%) (Table S1). The most common chromosome polymorphisms were 46,XN,inv(9)(p13q13) (n = 65; RF = 31.86%), followed by 46,X,Yqh+ (n = 36; RF = 17.65%), and 46,X,Y(Y < G) (n = 21; RF = 10.29%) (Table S1).
Main clinical manifestations and chromosomal abnormalities
Based on the clinical information of the patients, we divided them into infertile group (n = 1994), adverse pregnancy and parturition history group (n = 1520), growth and developmental abnormalities group (n = 322), congenital diseases and mental retardation group (n = 113) and other (n = 1340). There were statistically significant differences in the chromosomal abnormalities rate in infertile group (χ2 = 47.621, P < 0.001) and adverse pregnancy and parturition history group (χ2 = 47.353, P < 0.001), growth and developmental abnormalities group (χ2 = 10.740, P = 0.014), congenital diseases and mental retardation group (χ2 = 242.107, P < 0.001). The main types of chromosomal abnormalities were chromosome polymorphism (n = 79; ADR = 3.96%) and sex chromosome aneuploidy (n = 40; ADR = 2.01%) in infertile group, which chromosome polymorphism (n = 68; ADR = 4.47%) and structural abnormality (n = 36; ADR = 2.37%) in adverse pregnancy and parturition history group, chromosome polymorphism (n = 12; ADR = 3.73%) and sex chromosome aneuploidy (n = 12; ADR = 3.73%) in growth and developmental abnormalities group, and autosomal aneuploidy (n = 33; ADR = 29.20%) in congenital diseases and mental retardation group (Table 2).
Table 2
Main clinical manifestations and chromosomal abnormalities.
Group
|
Numerical abnormality
|
Structural abnormality
|
Chromosome polymorphism
|
Total (n, %)
|
P value
|
Autosomal Aneuploidy
|
Sex Chromosome Aneuploidy
|
Infertile (n = 1994)
|
0(0)
|
40(2.01)
|
16(0.80)
|
79(3.96)
|
135(6.77)
|
< 0.001(χ2 = 47.621)
|
Abnormal gestation and birth (n = 1520)
|
0(0)
|
3(0.20)
|
36(2.37)
|
68(4.47)
|
107(7.04)
|
< 0.001(χ2 = 47.353)
|
Growth and developmental abnormalities (n = 322)
|
2(0.62)
|
12(3.73)
|
5(1.55)
|
12(3.73)
|
31(9.63)
|
0.014 (χ2 = 10.740)
|
Congenital diseases and mental retardation (n = 113)
|
33(29.20)
|
3(2.65)
|
4(3.54)
|
4(3.54)
|
44(38.94)
|
< 0.001(χ2 = 242.107)
|
Other (n = 1340)
|
3(0.22)
|
10(0.75)
|
21(1.57)
|
41(3.06)
|
75(5.60)
|
0.098(χ2 = 6.309)
|
Chromosomal abnormalities of fetuses
Chromosomal abnormalities were detected in a total of 307 fetus samples, and the ADR was 10.65% (307/2,882), which 12.30% (47/382) in chorionic villus samples, 10.71% (254/2,372) in amniocentesis samples and 4.69% (6/128) in cord blood samples. The ADR for sex chromosome aneuploidies, autosomal aneuploidies, triploid/tetraploid, structural abnormalities and chromosome polymorphisms were 1.70% (49/2,882), 5.45% (157/2,882), 0.14% (4/2,882), 1.39% (40/2,882) and 1.94% (56/2,882), which 3.14% (12/382), 6.81% (26/382), 0.26% (1/382), 0.52% (2/382), 1.57% (6/382) for chorionic villus samples, 1.52% (36/2,372), 5.40% (128/2,372), 0.13% (3/2,372), 1.56% (37/2,372), 2.07% (49/2,372) for amniocentesis samples and 0.78% (1/128), 2.34% (3/128), 0.78% (1/128), 0.78% (1/128) for cord blood samples.
Among fetuses with chromosomal abnormalities, numerical abnormalities, chromosomal structural abnormalities and chromosome polymorphism accounted for 68.40% (210/307), 13.03% (40/307) and 18.24% (56/307), respectively. The most frequently seen numerical chromosomal abnormalities by RF were trisomy 21, trisomy 18, 45,XO, and 47,XXY at 36.16%, 11.07%, 5.86%, and 4.89%. The most frequently seen numerical chromosomal abnormalities were trisomy 21, trisomy 18, and 45,XO at 25.53%, 19.15%, and 19.15% in chorionic villus samples, which trisomy 21, trisomy 18, and 47,XXY at 38.19%, 9.45%, and 5.51% in amniocentesis samples (Table 3).
Table 3
Chromosomal abnormalities detected in prenatal diagnosis.
Chromosomal abnormalities
|
Chorionic villus samples (CVS) (n=382)
|
Amniocentesis (AC) (n=2372)
|
Cord blood (CB) (n=128)
|
Total (n=2882)
|
No. Abn Cases
|
ADR (%)
|
RF (%)
|
No. Abn Cases
|
ADR (%)
|
RF (%)
|
No. Abn Cases
|
ADR (%)
|
RF (%)
|
No. Abn Cases
|
ADR (%)
|
RF (%)
|
Numerical abnormality
Sex Chromosome Aneuploidy
|
|
|
|
|
|
|
|
|
|
|
|
|
45,XO
|
9
|
2.36
|
19.15
|
8
|
0.34
|
3.15
|
1
|
0.78
|
16.67
|
18
|
0.62
|
5.86
|
45,X[26]/46,XY[4]
|
0
|
0.00
|
0.00
|
1
|
0.04
|
0.39
|
0
|
0.00
|
0.00
|
1
|
0.03
|
0.33
|
47,XXX
|
1
|
0.26
|
2.13
|
5
|
0.21
|
1.97
|
0
|
0.00
|
0.00
|
6
|
0.21
|
1.95
|
47,XXY
|
1
|
0.26
|
2.13
|
14
|
0.59
|
5.51
|
0
|
0.00
|
0.00
|
15
|
0.52
|
4.89
|
47,XXY[13]/46,XX[87]
|
1
|
0.26
|
2.13
|
0
|
0.00
|
0.00
|
0
|
0.00
|
0.00
|
1
|
0.03
|
0.33
|
47,XXY[16]/46,XY[34]
|
0
|
0.00
|
0.00
|
1
|
0.04
|
0.39
|
0
|
0.00
|
0.00
|
1
|
0.03
|
0.33
|
47,XYY
|
0
|
0.00
|
0.00
|
5
|
0.21
|
1.97
|
0
|
0.00
|
0.00
|
5
|
0.17
|
1.63
|
48,XXXY
|
0
|
0.00
|
0.00
|
1
|
0.04
|
0.39
|
0
|
0.00
|
0.00
|
1
|
0.03
|
0.33
|
48,XXYY
|
0
|
0.00
|
0.00
|
1
|
0.04
|
0.39
|
0
|
0.00
|
0.00
|
1
|
0.03
|
0.33
|
Subtotal
|
12
|
3.14
|
25.53
|
36
|
1.52
|
14.17
|
1
|
0.78
|
16.67
|
49
|
1.70
|
15.96
|
Autosomal Aneuploidy
|
|
|
|
|
|
|
|
|
|
|
|
|
Trisomy 21
|
12
|
3.14
|
25.53
|
97
|
4.09
|
38.19
|
2
|
1.56
|
33.33
|
111
|
3.85
|
36.16
|
Trisomy 18
|
9
|
2.36
|
19.15
|
24
|
1.01
|
9.45
|
1
|
0.78
|
16.67
|
34
|
1.18
|
11.07
|
Trisomy 13
|
2
|
0.52
|
4.26
|
6
|
0.25
|
2.36
|
0
|
0.00
|
0.00
|
8
|
0.28
|
2.61
|
Other aneuploidy
|
3
|
0.79
|
6.38
|
1
|
0.04
|
0.39
|
0
|
0.00
|
0.00
|
4
|
0.14
|
1.30
|
Subtotal
|
26
|
6.81
|
55.32
|
128
|
5.40
|
50.39
|
3
|
2.34
|
50.00
|
157
|
5.45
|
51.14
|
Triploid & tetraploid
|
1
|
0.26
|
2.13
|
3
|
0.13
|
1.18
|
0
|
0.00
|
0.00
|
4
|
0.14
|
1.30
|
Total
|
39
|
10.21
|
82.98
|
167
|
7.04
|
65.75
|
4
|
3.13
|
66.67
|
210
|
7.29
|
68.40
|
Structural abnormality
|
2
|
0.52
|
4.26
|
37
|
1.56
|
14.57
|
1
|
0.78
|
16.67
|
40
|
1.39
|
13.03
|
Chromosome polymorphism
|
6
|
1.57
|
12.77
|
49
|
2.07
|
19.29
|
1
|
0.78
|
16.67
|
56
|
1.94
|
18.24
|
mos46,XX[28]/46,XY[22]
|
0
|
0.00
|
0.00
|
1
|
0.04
|
0.39
|
0
|
0.00
|
0.00
|
1
|
0.03
|
0.33
|
All chromosomal abnormalities
|
47
|
12.30
|
100.00
|
254
|
10.71
|
100.00
|
6
|
4.69
|
100.00
|
307
|
10.65
|
100.00
|
ADR, abnormality detection rate (%); RF, relative frequency by (%); *Statistically different from ADR in prenatal setting (P< 0.05)
The most common structural chromosomal abnormalities were 46,X,inv(Y)(p11.2q11.23) (n = 4; RF = 10.0%), followed by 46,XN,dup(1)(q11q12) (n = 3; RF = 7.5%), and 46,XN,dup(1)(q11q21) (n = 2; RF = 5.0%) (Table S2). The most common chromosome polymorphisms were 46,XN,inv(9)(p13q13) (n = 28; RF = 50.0%), followed by 46,XN,inv(9)(p11q13) (n = 2; RF = 3.57%), and 46,XN,inv(9)(p13q13) (n = 2; RF = 3.57%) (Table S2).
The relationship of maternal age, gestational age and chromosomal abnormalities
Based on the age of the pregnant women, the cases included in this study were divided into less than 35 years old group and greater than or equal to 35 years old group. There were statistically significant differences in the chromosomal abnormalities rate between this two groups (χ2 = 51.041, P < 0.001). The main types of chromosomal abnormalities were autosomal aneuploidy (n = 88; ADR = 3.89%) and chromosome polymorphism (n = 49; ADR = 2.16%) in less than 35 years old group, which autosomal aneuploidy (n = 69; ADR = 11.18%) and sex chromosome aneuploidy (n = 16; ADR = 2.59%) in greater than or equal to 35 years old group. Grouped according to gestational age, there were no significant differences in the chromosomal abnormalities rate in < 13 weeks group, 13–28 weeks group and > 28 weeks group (Table 4).
Table 4
Comparison of karyotype abnormalities at different maternal ages and gestational weeks.
Group
|
Numerical abnormality
|
Structural abnormality
|
Chromosome polymorphism
|
Total (n, %)
|
P value
|
Autosomal Aneuploidy
|
Sex Chromosome Aneuploidy
|
Triploid & tetraploid
|
Maternal age
|
|
|
|
|
|
|
|
< 35 years (n = 2264)
|
88(3.89)
|
33(1.46)
|
4(0.18)
|
29(1.28)
|
49(2.16)
|
203(8.97)
|
< 0.001(χ2 = 51.041)
|
≥ 35 years (n = 617)
|
69(11.18)
|
16(2.59)
|
0(0)
|
11(1.78)
|
7(1.13)
|
103(16.69)
|
Gestational age
|
|
|
|
|
|
|
|
< 13 weeks (n = 268)
|
16(5.97)
|
7(2.61)
|
1(0.37)
|
2(0.75)
|
6(2.24)
|
32(11.94)
|
0.428(χ2 = 4.579)
|
13–28 weeks (n = 2462)
|
140(5.69)
|
40(1.62)
|
3(0.12)
|
36(1.46)
|
47(1.91)
|
266(10.80)
|
0.515(χ2 = 4.023)
|
> 28 weeks (n = 151)
|
1(0.66)
|
2(1.32)
|
0(0)
|
2(1.32)
|
3(1.99)
|
8(5.30)
|
0.069(χ2 = 9.645)
|