SNP-array分析在颈项皮肤皱褶增厚胎儿遗传学诊断中的应用

梁志坤; 李明艺; 邓蕊; 黄敏; 谢波波; 欧阳鲁平

doi:10.16766/j.cnki.issn.1674-4152.001788

SNP-array分析在颈项皮肤皱褶增厚胎儿遗传学诊断中的应用

doi: 10.16766/j.cnki.issn.1674-4152.001788

1.
广西壮族自治区妇幼保健院检验科，广西南宁 530003
2.
广西壮族自治区妇幼保健院遗传代谢中心实验室，广西南宁 530003

基金项目:

国家重点研发计划 2017YFC1001703

广西壮族自治区卫健委自筹课题 Z20200643

详细信息

通讯作者:
梁志坤，E-mail：2304199358@qq.com

中图分类号: R714.5 R446
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- 被引次数: 0
出版历程
- 收稿日期: 2020-04-23
- 网络出版日期: 2022-02-19

Application of single nucleotide polymorphism microarray in genetic diagnosis of nuchal fold thickened fetuses

1.
Clinical Laboratory, Maternal & Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530003, China

摘要

摘要: 目的探讨胎儿颈部皮肤皱褶(nuchal fold，NF)增厚的产前诊断与遗传咨询。方法回顾性分析2018年1月—2019年8月间来广西壮族自治区妇幼保健院产科产检，超声检查提示孕中期16~18孕周NF≥5.0 mm；19~22孕周NF≥6.0 mm的152例NF增厚的孕妇，行羊膜腔穿刺抽取羊水标本，同时行羊水细胞核型分析和染色体微阵列芯片技术(single nucleotide polymorphism array，SNP-array)检测，统计这些孕妇的临床诊断资料，并分析胎儿染色体核型分析与染色体微阵列芯片检测结果。结果 152例NF增厚胎儿标本中，检出染色体核型异常19例，检出率为12.5%(19/152)。19例异常核型中21-三体：12例；18-三体：2例；45，X：2例；47，XXX：1例；嵌合体45, -6[28]/46, r(6)(p25q26)[12]：1例；46, XN, del(5)(p14)：1例。SNP-array检出33例异常，检出率为21.71%(33/152)，SNP-array技术的检出率明显高于核型分析的异常检出率。除了能检出核型分析发现的染色体非整倍体或大片段结构异常外，SNP-array技术还检出染色体核型分析未能检出的14例微缺失，其中4例致病性拷贝数变异，2例可疑致病性拷贝数变异，其余8例为临床意义不明拷贝数变异病例。结论对超声筛查为胎儿颈背皮肤皱褶增厚的病例，SNP-array技术诊断可明显提高染色体核型分析未能检测出的染色体亚显微结构的畸变。
- 颈项皮肤皱褶增厚 /
- 羊膜腔膜穿刺 /
- 单核苷酸多态性微阵列芯片 /
- 核型分析
Abstract: Objective To discuss the prenatal diagnosis and genetic counseling of nuchal fold (NF) thickened fetuses. Methods A retrospective analysis was performed on 152 pregnant women with NF ≥ 5.0 mm at 16-18 gestational weeks and NF ≥ 6.0 mm at 19-22 gestational weeks From January 2018 to July 2019 in Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region. Amniotic fluid samples were obtained by amniocentesis, and chromosome karyotype analysis and single nucleotide polymorphism array (SNP-array) were performed at the same time. Clinical diagnostic data of these pregnant women were collected, and fetal chromosome karyotype analysis and chromosome microarray detection results were analyzed. Results Among the 152 cases of nuchal fold thickened fetuses, 19 cases (19/152, 12.5%) of chromosomal karyotype abnormalities were detected. Among the 19 abnormal karyotypes, there were 12 cases of trisomy 21, 2 cases of trisomy 18, 2 cases of 45, X, 1 cases of 47, XXX, 1 cases of 45, -6[28]/46, r(6)(p25q26)[12], and 1 case of 46, XN, del (5) (p14). There were 33 abnormal cases detected by SNP-array, with a detection rate of 21.71% (33/152). The SNP-array detection rate was significantly higher than that of chromosome karyotype. In addition to the aneuploid or large fragment structural abnormalities detected by karyotype detection, the SNP-array also detected 14 cases of microdeletions not detected by karyotype analysis, including 4 cases of pathogenic copy number variation, 2 cases of suspected pathogenic copy number variation, and 8 cases of unknown clinical significance copy number variation. Conclusion For the nuchal fold thickened fetuses screened by ultrasound, SNP array technique can significantly improve the chromosome ultrastructure aberrations which cannot be detected by karyotype analysis.
- Nuchal fold thickened /
- Amniocentesis /
- Single nucleotide polymorphism array /
- Karyotype analysis

HTML全文

表 1 14例SNP部分微缺失、微重复的阳性结果

病例	芯片结果	类型	染色体片段大小(Mb)	致病性	妊娠结局
1	arr 16p13.3(216738-271712)x0	缺失	0.05	致病	终止妊娠
2	arr17q12(34628791-36249565)x1	缺失	1.62	致病	终止妊娠
3	arrXp21.1(32042961-32278101)x0	缺失	0.23	致病	终止妊娠
4	UPD(1-22，X)pat.arr(1-22，X)x2	UPD		致病	失访
5	arr2p21p13.3(46327709-70173327)x2 hmz, 7q21.1q22.1(85558378-98394810)x2 hmz	杂合性缺失	23.85/12.84	可疑致病	顺产，外观未见异常
6	arrYp11.31p11.2(2654900-9645003)x1	缺失	6.99	可疑致病	剖宫产，外观未见异常
7	arr1q23.1(157, 386, 331-158, 668, 378)x3	重复	1.28	临床意义不明	顺产，外观未见异常
8	arr2p12(78467412-80059495)x3	重复	1.59	临床意义不明	顺产，外观未见异常
9	涉及到2号、3号、5号、6号、8号、9号、10、13号、17号、22号染色体的杂合性缺失	杂合性缺失		临床意义不明	失访
10	arr 12p11.21(31005429-31351285)x1	缺失	0.34	临床意义不明	顺产，外观未见异常
11	arr 12q24.32(127353820-128960679)x3	重复	1.61	临床意义不明	顺产，外观未见异常
12	arr 16p12.1(25211679-26466080)x3	重复	1.25	临床意义不明	剖宫产，外观未见异常
13	arr Xp22.31(6516735-8131442)x3	重复	1.61	临床意义不明	顺产，外观未见异常
14	arrXp22.31(6532072-8141017)x1	缺失	1.60	临床意义不明	顺产，外观未见异常
注：UPD为单亲二倍体。

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