SNP array在颈项透明层增厚胎儿产前诊断中的应用

doi:10.3969/j.issn.1673-8640.2020.02.011

摘要/Abstract

摘要：

目的探讨单核苷酸多态性微阵列技术（SNP array）在颈项透明层（NT）增厚胎儿产前诊断中的应用。方法选取孕11~13⁺⁶周NT厚度超过2.5 mm并全部接受SNP array与多重定量荧光聚合酶链反应（QF-PCR）检测的胎儿433例。根据NT厚度分为4个组（A组2.5~3.4 mm、B组3.5~4.4 mm、C组4.5~5.5 mm、D组≥5.5 mm）,根据是否合并其他超声异常进一步分为单纯性NT增厚组和合并其他超声异常组。结果 QF-PCR共检出染色体数目异常49例（11.32 %）,除1例嵌合体外,检出了SNP array检出的所有数目异常。SNP array染色体数目异常检出率为11.55%,A~D组分别为4.64%、11.36%、26.42%、22.2%;致病性拷贝数变异（pCNV）异常检出率为3.46%（15/433）,A~D组分别为1.0%、4.5%、3.8%、9.3%。单纯性NT增厚组染色体数目异常率、pCNV异常率分别为9.91%、2.14%,合并其他超声异常组分别为21.67%和11.67%。存在pCNV与仅有非pCNV孕妇无年龄差别。结论 NT厚度及是否合并其他超声异常对染色体数目异常及pCNV均有影响,宜采用NT厚度3.5 mm为截断值。应联合多重QF-PCR与SNP array对孕早期NT增厚胎儿进行快速、准确的产前诊断。

关键词: 颈项透明层增厚, 单核苷酸多态性微阵列技术, 多重定量荧光聚合酶链反应, 非整倍体, 拷贝数变异

Abstract:

Objective To investigate the application of single nucleotide polymorphism（SNP） array for fetuses with thickened nuchal translucency（NT）. Methods A total of 433 fetuses whose NT thickness was over 2.5 mm at 11-13⁺⁶ weeks of gestation were enrolled and determined by SNP array and multiple quantitation fluorescence polymerase chain reaction（QF-PCR）. The fetuses were classified into 4 groups according to the thickness of NT（2.5-3.4 mm in group A,3.5-4.4 mm in group B,4.5-5.5 mm in group C and ≥5.5 mm in group D）and classified into 2 groups according to whether combined with other ultrasonic abnormalities（simple NT thickening group and combined with other ultrasonic abnormality group）. Results A total of 49 cases（11.32%） of chromosome number abnormalities were determined by multiple QF-PCR,and all of the abnormalities were determined by SNP array except 1 case of chimera. Abnormal chromosome number was 11.55% as a whole,accounting for 4.64%,11.36%,26.42% and 22.2% in group A to group D,respectively. Pathogenic copy number variations（pCNV） were 3.46% as a whole,accounting for 1.0%,4.5%,3.8% and 9.3% in group A to group D,respectively. The rate of chromosome number abnormalities was 9.91%,and that of pCNV was 2.14% in simple NT thickening group. The rate of chromosome number abnormalities was 21.67%,and that of pCNV was 11.67% in combined with other ultrasonic abnormality group. There was no statistical significance for age between pregnant women with pCNV or not. Conclusions The thickness of NT and whether combined with other ultrasonic abnormalities have impact on chromosome number and pCNV variation. The thickness of NT should be cut-off as 3.5 mm.

Key words: Thickened nuchal translucency, Single nucleotide polymorphism array, Multiple quantitation fluorescence polymerase chain reaction, Aneuploidy, Copy number variation

中图分类号:

R446.1

李瑞, 时盼来, 王爱玲, 王建红, 肖艳华, 孔祥东. SNP array在颈项透明层增厚胎儿产前诊断中的应用[J]. 检验医学, 2020, 35(2): 142-147.

LI Rui, SHI Panlai, WANG Ailing, WANG Jianhong, XIAO Yanhua, KONG Xiangdong. Application of single nucleotide polymorphism array for fetuses with thickened nuchal translucency[J]. Laboratory Medicine, 2020, 35(2): 142-147.

图/表 5

参考文献 18

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项目	多重QF-PCR	SNP array
数目变异
47,XN,+21	28（6.47）	28（6.47）
47,XN,+18	9（2.08）	9（2.08）
45,XO	5（1.15）	5（1.15）
47,XN,+13	1^*	1^*
47,XXX	1^*	1^*
49,XXXXY	1^*	1^*
47,XXY	1^*	1^*
48,XXY,+21	1^*#	1^*
47,XN,+21;Xp22.31 （6532072-8091350）×3	1^*#	1^*
47,XN,+22/46,XN	0	1^*
48,XY,+8,162hmz, +21/47,XY, 162hmz,+21	1^*#	1^*
合计	49（11.32）	50（11.55）
正常	384	383
结构变异
pCNV	0	15（3.46）
VOUS	0	22（5.08）
UPD	0	1^*
正常	433	395

项目	多重QF-PCR	SNP array
数目变异
47,XN,+21	28（6.47）	28（6.47）
47,XN,+18	9（2.08）	9（2.08）
45,XO	5（1.15）	5（1.15）
47,XN,+13	1^*	1^*
47,XXX	1^*	1^*
49,XXXXY	1^*	1^*
47,XXY	1^*	1^*
48,XXY,+21	1^*#	1^*
47,XN,+21;Xp22.31 （6532072-8091350）×3	1^*#	1^*
47,XN,+22/46,XN	0	1^*
48,XY,+8,162hmz, +21/47,XY, 162hmz,+21	1^*#	1^*
合计	49（11.32）	50（11.55）
正常	384	383
结构变异
pCNV	0	15（3.46）
VOUS	0	22（5.08）
UPD	0	1^*
正常	433	395

组别	例数	染色体数目异常	pCNV阳性
A组	194	9（4.64）	2（1.0）
B组	132	15（11.36）^**	6（4.5）^*
C组	53	14（26.42）^**	2（3.8）^*
D组	54	12（22.20）^**	5（9.3）^*
χ²值		26.564	9.204
P值		0.000	0.016

组别	例数	染色体数目异常	pCNV阳性
A组	194	9（4.64）	2（1.0）
B组	132	15（11.36）^**	6（4.5）^*
C组	53	14（26.42）^**	2（3.8）^*
D组	54	12（22.20）^**	5（9.3）^*
χ²值		26.564	9.204
P值		0.000	0.016

组别	例数	染色体数目异常	pCNV阳性
单纯性NT增厚组	373	37（9.91）	8（2.14）
合并其他超声异常组	60	13（21.67）	7（11.67）
χ²值		7.35
P值		0.007	0.002