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浙江大学学报（医学版）
浙江大学学报（医学版）  2019, Vol. 48 Issue (4): 414-419    DOI: 10.3785/j.issn.1008-9292.2019.08.11
专题报道     
74例鼻骨缺失胎儿单核苷酸多态性微阵列检测结果分析
俞佳玲(),孙义锡,胡珺洁,钱叶青,罗玉琴,董旻岳*()
浙江大学医学院附属妇产科医院生殖遗传科 生殖遗传教育部重点实验室, 浙江 杭州 310006
Single nucleotide polymorphism microarray in prenatal diagnosis of fetuses with absent nasal bone
YU Jialing(),SUN Yixi,HU Junjie,QIAN Yeqing,LUO Yuqin,DONG Minyue*()
Key Laboratory of Reproductive Genetics, Ministry of Education, Department of Reproductive Genetics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
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摘要：

目的: 评估单核苷酸多态性微阵列分析在胎儿鼻骨缺失遗传学产前诊断中的效用。方法: 以2015年6月至2018年10月在浙江大学医学院附属妇产科医院因鼻骨缺失行染色体核型及单核苷酸多态性微阵列分析的74例孕妇为研究对象，分析胎儿鼻骨缺失及是否合并其他超声检查异常与染色体拷贝数异常的关系。结果: 74例鼻骨缺失的胎儿中共检出染色体异常19例，其中21三体综合征16例，18三体综合征1例，染色体微重复/缺失2例。在46例不合并其他超声检查异常的单纯鼻骨缺失的病例中，21三体综合征3例，染色体微缺失1例。鼻骨缺失合并颈项透明层增厚的胎儿染色体异常的比例高于仅鼻骨缺失组胎儿（χ2=32.27，P < 0.01）。结论: 胎儿鼻骨缺失合并颈项透明层增厚增加染色体异常的风险，应进一步行染色体核型及单核苷酸多态性微阵列分析以排除染色体异常的可能。
关键词： 鼻骨/畸形;  染色体;  多态性, 单核苷酸;  微阵列分析;  异常核型;  超声检查, 产前;  颈部透明带检查;  颈/病理学    
Abstract:

Objective: To assess the clinical application of single nucleotide polymorphism microarray (SNP array) in prenatal genetic diagnosis for fetuses with absent nasal bone. Methods: Seventy four fetuses with absent nasal bone detected by prenatal ultrasound scanning were recruited from Women's Hospital, Zhejiang University School of Medicine during June 2015 and October 2018. The chromosome karyotypes analysis and SNP array were performed. The correlation between absent fetal nasal bone and chromosome copy number variants was analyzed. Results: Among 74 fetuses, 19 were detected to have chromosomal abnormalities, including 16 cases of trisomy-21, 1 case of trisomy-18 and two cases of micro-deletion/duplication. Among 46 cases with isolated absence of nasal bone, 3 had trisomy-21, and 1 had a micro-duplication. Absence of nasal bone in association with nuchal translucency thickening had a higher rate of abnormal karyotypes compared with isolated absence of nasal bone (χ2=32.27, P < 0.01). Conclusion: Fetuses with absent nasal bone and nuchal translucency thickening are likely to have chromosome abnormalities, and SNP array testing is recommended to exclude the chromosome abnormalities.
Key words: Nasal bone/abnormalities    Chromosomes    Polymorphism, single nucleotide    Microarray analysis    Abnormal karyotype    Ultrasonography, prenatal    Nuchal translucency measurement    Neck/pathology
收稿日期: 2019-03-28 出版日期: 2019-10-30
:  R394.3  
基金资助: 国家重点研发计划(2016YFC1000703);浙江省重大研发计划(2019C03025);浙江省医药卫生科技计划(2019313572)
通讯作者: 董旻岳     E-mail: jialingyu@zju.edu.cn;dongmy@zju.edu.cn
作者简介: 俞佳玲(1989—), 女, 博士, 助理研究员, 主要从事遗传学研究; E-mail: jialingyu@zju.edu.cn; https://orcid.org/0000-0002-9836-910X
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引用本文:

俞佳玲,孙义锡,胡珺洁,钱叶青,罗玉琴,董旻岳. 74例鼻骨缺失胎儿单核苷酸多态性微阵列检测结果分析[J]. 浙江大学学报（医学版）, 2019, 48(4): 414-419.

YU Jialing,SUN Yixi,HU Junjie,QIAN Yeqing,LUO Yuqin,DONG Minyue. Single nucleotide polymorphism microarray in prenatal diagnosis of fetuses with absent nasal bone. J Zhejiang Univ (Med Sci), 2019, 48(4): 414-419.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2019.08.11    或    http://www.zjujournals.com/med/CN/Y2019/V48/I4/414

序号 孕妇年龄 样品类型 超声异常表现 SNP array检测结果 核型分析结果
“—”无相关资料；NT：颈项透明层；SNP array:单核苷酸多态性微阵列.
1 31 羊水 NT为3.5 mm arr(21)×3 47, XN+21
2 24 脐血 胎儿侧脑室增宽，局部肠管回声增强，室间隔缺损 arr(21)×3 47, XN+21
3 34 绒毛 NT为6.5 mm arr(18)×3 —
4 38 羊水 NT为3.2 mm arr(21)×3 47, XN+21
5 30 产前绒毛 NT为3.5 mm arr(21)×3 47, XN+21
6 41 羊水 NT为3.7 mm arr(21)×3, arr[hg19]4p16.3(68 345~694 965)×1 47, XN+21
7 43 羊水 NT为3.1 mm arr(21)×3 47, XN+21
8 35 脐血 NT为3.2 mm，左心房强光斑 arr(21)×3 47, XN+21
9 28 组织 NT为3.2 mm arr(21)×3 —
10 29 羊水 NT为3.5 mm arr[hg19]15q14q15.1(37 447 597~41 698 882)×3 未见明显异常
11 38 羊水 NT为3.0 mm arr(21)×3 47, XN+21
12 36 脐血 胎儿双侧侧脑室增宽 arr(21)×3 47, XN+21
13 28 脐血 — arr[hg19]16p13.11(14 888 582~16 544 222)×1 未见明显异常
14 35 羊水 — arr(21)×3 47, XN+21
15 20 脐血 — arr(21)×3, arr[hg19]2q13(110 504 318~ 111 365 996)×1 47, XN+21
16 26 脐血 双足第四趾重叠 arr(21)×3 47, XN+21
17 42 羊水 NT为4.1 mm arr(21)×3 47, XN+21
18 42 羊水 NT为1.7 mm arr(21)×3 47, XN+21
19 38 羊水 NT为3.9 mm arr(21)×3 47, XN+21
表 1  19例染色体异常的鼻骨缺失胎儿超声异常表现和遗传学检测结果
(n)
组别 n 21三体综合征 18三体综合征 染色体微重复/缺失(>1 Mb) 合计
*颈项透明层(NT)≥3.0 mm；#包括双侧脉络丛囊肿、左心室内多发强光斑、四肢长骨偏短、局部肠管回声增强；△包括室间隔缺损、心脏横纹肌瘤、胎儿双足内翻、左肾异位肾、双足第四趾重叠.
单纯鼻骨缺失组 46 3 0 1 4
鼻骨缺失合并NT增厚* 15 10 1 1 12
鼻骨缺失合并其他超声软指标异常# 6 1 0 0 1
鼻骨缺失合并结构异常△ 7 2 0 0 2
表 2  74例鼻骨缺失合并不同超声检查异常胎儿染色体异常情况比较
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