Application of a modified copy number variation detection technique in spontaneous miscarriage heredity

doi:10.3969/j.issn.1673-8640.2019.07.015

Abstract

Abstract:

Objective To investigate the role of a high-throughput multiplex gene copy number variation detection technique（CNVplex） in spontaneous miscarriage heredity during early pregnancy. Methods Chorionic villus samples from 196 cases of spontaneous miscarriage were collected and divided into 2 groups after removing the decidua. One group was detected by chromosome karyotype analysis,and the other group was detected by CNVplex. The results were compared and analyzed. Results Among the 196 cases of chorionic villus samples,chorionic villus was successfully cultured in 175 cases（89.29%）,and abnormal karyotypes were detected in 98 cases（56%）,including 96 cases of chromosome number abnormalities and 2 cases of structural abnormalities. A total of 194 cases were successfully detected by CNVplex（98.98%）,and 115 cases of copy number abnormalities（59.29%）,including 107 cases of aneuploidy and 8 cases of chromosome segment copy number abnormalities,were detected. Among the 21 cases failed in karyotype analysis,CNVplex detected 16 cases of chromosome copy number abnormalities. In the 175 cases that were analyzed successfully in both methods,10 cases showed inconsistency,and there were 2 cases of polyploidy,2 cases of chimera and 1 case of translocation trisomy 22 recognized by karyotype analysis,while it was beyond the CNVplex detection scope. The other 5 cases of structure aberration identified by CNVplex were missed in karyotype analysis,and the results were then verified by parents' karyotype and fluorescence in situ hybridization（FISH）. Conclusions CNVplex has high detection success rate,it can effectively detect the copy number variation of small chromosome segments and greatly facilitates classical cytogenetics in the rapid detection of spontaneous miscarriage heredity during early pregnancy.

Key words: Spontaneous miscarriage, Copy number variation, Karyotype analysis

CLC Number:

R446.1

HU Wenjing, CHEN Qinfang, WU Yi, HAN Xu, GUO Xiaokui, TAO Jiong. Application of a modified copy number variation detection technique in spontaneous miscarriage heredity[J]. Laboratory Medicine, 2019, 34(7): 637-642.

Figures/Tables 4

References 17

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核型结果	染色体核型分析	检出率[%（例/例）]	CNVplex	检出率[%（例/例）]
46,XX/46,XY	77	44.00（77/175）	79	40.72（79/194）
非整倍体	88	50.29（88/175）	103	53.09（103/194）
多倍体	2	1.14（2/175）	0	0（0/194）
嵌合	6	3.43（6/175）	4	2.06（4/194）
结构异常	2	1.14（2/175）	8	4.12（8/194）
检测失败	21	10.71（21/196）	2	1.02（2/196）^*

核型结果	染色体核型分析	检出率[%（例/例）]	CNVplex	检出率[%（例/例）]
46,XX/46,XY	77	44.00（77/175）	79	40.72（79/194）
非整倍体	88	50.29（88/175）	103	53.09（103/194）
多倍体	2	1.14（2/175）	0	0（0/194）
嵌合	6	3.43（6/175）	4	2.06（4/194）
结构异常	2	1.14（2/175）	8	4.12（8/194）
检测失败	21	10.71（21/196）	2	1.02（2/196）^*

样本号	核型分析	CNVplex	验证方法与结果
104	69,XXX	46,XX
68	92,XXYY	46,XY
129	47,XX,+16[30]/ 46,XX^[10]	47,XX,+16	STR检测未发现母体细胞污染
141	47,XY,+16[29]/ 46,XX^[5]	47,XY,+16	STR检测未发现母体细胞污染
127	46,XY,i（22）（q10）	47,XY,+22
79	46,XX,der（8）?	46,XX.rsa 6q13×3,6q25.1×3,6q25.3×3, 6q27×3,8p23.3×1,8p23.1×1^*	母亲外周血染色体核型：46,XX,t （6;8）（q13;p23.1）
99	46,XY	46,XY.rsa 1p36.33×1,1p36.22×1.1p36.12×1, 16p13.3×3,16p13.2×1	母亲外周血染色体核型：46,XX,t （1;16）（p36.1;p13.2）
111	46,XX	46,XX.rsa 18q21.32×3,18q22.2×3, 18q23×1	FISH：ish（CEP18×2,Tel18q×1）
119	46,XX	46,XX.rsa 1p36.33×1,1p36.22×1, 1q42.13×3,1q43×3,1q44×3	FISH：ish（CEP1×2,Tel1p×1, Tel1q×3）
238	46,XX	46,XX,rsa 10q26.13×1,10q26.3×1, 14q31.3×3,14q32.2×3,14q32.33×3	FISH：ish（CEP14×2,Tel10q×1, Tel14q×3）

样本号	核型分析	CNVplex	验证方法与结果
104	69,XXX	46,XX
68	92,XXYY	46,XY
129	47,XX,+16[30]/ 46,XX^[10]	47,XX,+16	STR检测未发现母体细胞污染
141	47,XY,+16[29]/ 46,XX^[5]	47,XY,+16	STR检测未发现母体细胞污染
127	46,XY,i（22）（q10）	47,XY,+22
79	46,XX,der（8）?	46,XX.rsa 6q13×3,6q25.1×3,6q25.3×3, 6q27×3,8p23.3×1,8p23.1×1^*	母亲外周血染色体核型：46,XX,t （6;8）（q13;p23.1）
99	46,XY	46,XY.rsa 1p36.33×1,1p36.22×1.1p36.12×1, 16p13.3×3,16p13.2×1	母亲外周血染色体核型：46,XX,t （1;16）（p36.1;p13.2）
111	46,XX	46,XX.rsa 18q21.32×3,18q22.2×3, 18q23×1	FISH：ish（CEP18×2,Tel18q×1）
119	46,XX	46,XX.rsa 1p36.33×1,1p36.22×1, 1q42.13×3,1q43×3,1q44×3	FISH：ish（CEP1×2,Tel1p×1, Tel1q×3）
238	46,XX	46,XX,rsa 10q26.13×1,10q26.3×1, 14q31.3×3,14q32.2×3,14q32.33×3	FISH：ish（CEP14×2,Tel10q×1, Tel14q×3）