Please wait a minute...
J Zhejiang Univ (Med Sci)  2019, Vol. 48 Issue (4): 414-419    DOI: 10.3785/j.issn.1008-9292.2019.08.11
    
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
Download: HTML( 3 )   PDF(905KB)
Export: BibTeX | EndNote (RIS)      

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 wordsNasal bone/abnormalities      Chromosomes      Polymorphism, single nucleotide      Microarray analysis      Abnormal karyotype      Ultrasonography, prenatal      Nuchal translucency measurement      Neck/pathology     
Received: 28 March 2019      Published: 30 October 2019
CLC:  R394.3  
Corresponding Authors: DONG Minyue     E-mail: jialingyu@zju.edu.cn;dongmy@zju.edu.cn
Cite this article:

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.

URL:

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


74例鼻骨缺失胎儿单核苷酸多态性微阵列检测结果分析

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 
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
Tab 1 Summary of the 19 fetuses with absent nasal bone identified with chromosomal abnormalities by genetic aminocentesis
(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
Tab 2 Chromosomal abnormalities among fetuses with absent nasal bone combined with different ultrasound anormalies
[1]   VOS F I , DE JONG-PLEIJ E A , BAKKER M et al. Fetal facial profile markers of Down syndrome in the second and third trimesters of pregnancy[J]. Ultrasound Obstet Gynecol, 2015, 46 (2): 168- 173
doi: 10.1002/uog.14720
[2]   KAGAN K O , SONEK J , BERG X et al. Facial markers in second- and third-trimester fetuses with trisomy 18 or 13, triploidy or Turner syndrome[J]. Ultrasound Obstet Gynecol, 2015, 46 (1): 60- 65
doi: 10.1002/uog.14655
[3]   CICERO S , CURCIO P , PAPAGEORGHIOU A et al. Absence of nasal bone in fetuses with trisomy 21 at 11-14 weeks of gestation:an observational study[J]. Lancet, 2001, 358 (9294): 1665- 1667
doi: 10.1016/S0140-6736(01)06709-5
[4]   MORENO-CID M , RUBIO-LORENTE A , RODRí-GUEZ M J et al. Systematic review and meta-analysis of performance of second-trimester nasal bone assessment in detection of fetuses with Down syndrome[J]. Ultrasound Obstet Gynecol, 2014, 43 (3): 247- 253
doi: 10.1002/uog.13228
[5]   CICERO S , SONEK J D , MCKENNA D S et al. Nasal bone hypoplasia in trisomy 21 at 15-22 weeks' gestation[J]. Ultrasound Obstet Gynecol, 2003, 21 (1): 15- 18
doi: 10.1002/uog.19
[6]   戚庆炜, 张巍.胎儿NT增厚的临床意义和基于基因组学的遗传诊断路径分析[J/CD].妇产与遗传(电子版), 2017, 7(2): 50-54.
QI Qingwei, ZHANG Wei. Clinical significance of fetal NT hypertrophy and genetic diagnosis pathway based on genomics[J/CD]. Obstetrics-Gynecology and Genetics (Electronic Edition), 2017, 7(2): 50-54. (in Chinese)
[7]   TING Y H , LAO T T , LAU T K et al. Isolated absent or hypoplastic nasal bone in the second trimester fetus:is amniocentesis necessary?[J]. J Matern Fetal Neonatal Med, 2011, 24 (4): 555- 558
doi: 10.3109/14767058.2010.487140
[8]   DU Y , REN Y , YAN Y et al. Absent fetal nasal bone in the second trimester and risk of abnormal karyotype in a prescreened population of Chinese women[J]. Acta Obstet Gynecol Scand, 2018, 97 (2): 180- 186
doi: 10.1111/aogs.13263
[9]   GRUCHY N , DECAMP M , RICHARD N et al. Array CGH analysis in high-risk pregnancies:comparing DNA from cultured cells and cell-free fetal DNA[J]. Prenat Diagn, 2012, 32 (4): 383- 388
doi: 10.1002/pd.2861
[10]   D'AMOURS G , KIBAR Z , MATHONNET G et al. Whole-genome array CGH identifies pathogenic copy number variations in fetuses with major malformations and a normal karyotype[J]. Clin Genet, 2012, 81 (2): 128- 141
doi: 10.1111/j.1399-0004.2011.01687.x
[11]   SHINAWI M , CHEUNG S W . The array CGH and its clinical applications[J]. Drug Discov Today, 2008, 13 (17-18): 760- 770
doi: 10.1016/j.drudis.2008.06.007
[12]   DUKHOVNY S , WILKINS-HAUG L , SHIPP T D et al. Absent fetal nasal bone:what does it mean for the euploid fetus?[J]. J Ultrasound Med, 2013, 32 (12): 2131- 2134
doi: 10.7863/ultra.32.12.2131
[13]   SMITH A E , JNAH A , NEWBERRY D . Chromosome 16p13.11 microdeletion syndrome in a newborn:a case study[J]. Neonatal Netw, 2018, 37 (5): 303- 309
doi: 10.1891/0730-0832.37.5.303
[14]   LAW L W , LAU T K , FUNG T Y et al. De novo 16p13.11 microdeletion identified by high-resolution array CGH in a fetus with increased nuchal translucency[J]. BJOG, 2009, 116 (2): 339- 343
doi: 10.1111/j.1471-0528.2008.01948.x
[1] HU Junjie,QIAN Yeqing,SUN Yixi,YU Jialing,LUO Yuqin,DONG Minyue. Application of single nucleotide polymorphism microarray in clinical diagnosis of intellectual disability or retardation[J]. J Zhejiang Univ (Med Sci), 2019, 48(4): 420-428.
[2] WANG Yayun,CHEN Yuan,YANG Mengmeng,XI Fangfang,ZHAN Qitao,JIANG Ying,ZHAO Baihui,LUO Qiong. Prognosis of fetuses with cystichygroma and nuchal translucency/nuchal fold thickening on prenatal echography[J]. J Zhejiang Univ (Med Sci), 2019, 48(4): 434-438.
[3] LEI Yu,DONG Minyue. Association of maternal age with fetal sex chromosome aneuploidies[J]. J Zhejiang Univ (Med Sci), 2019, 48(4): 409-413.
[4] YIN Yixuan,ZHU Hui,QIAN Yeqing,JIN Jinglei,MEI Jin,DONG Minyue. Noninvasive prenatal screening for twin pregnancy: an analysis of 2057 cases[J]. J Zhejiang Univ (Med Sci), 2019, 48(4): 403-408.
[5] YE Qing,ZHANG Yingying,WANG Jingjing,MAO Jianhua. Analysis of Alport syndrome induced by type IV collagen alpha 5 gene mutation in two families[J]. J Zhejiang Univ (Med Sci), 2019, 48(4): 384-389.
[6] MEI Jin,LIU Jiao,WANG Min,ZHANG Wen,WANG Hao,LU Sha,HE Chaying,JIN Chunlei. Prenatal diagnosis and pregnancy outcomes of 22q11.2 duplication syndrome: analysis of 8 cases[J]. J Zhejiang Univ (Med Sci), 2019, 48(4): 429-433.
[7] LUO Yuqin,SHEN Min,SUN Yixi,QIAN Yeqing,WANG Liya,YU Jialing,HU Junjie,JIN Fan,DONG Minyue. Genetic analysis of a fetus with multiple malformations caused by complex translocations of four chromosomes[J]. J Zhejiang Univ (Med Sci), 2019, 48(4): 397-402.
[8] HONG Pingping,GUO Bingjie,LIN Li,LIN Xihua,ZHOU Jiaqiang. A novel mutation W257R in GCK gene discovered from a Chinese patient with maturity onset diabetes of the young[J]. J Zhejiang Univ (Med Sci), 2019, 48(2): 200-203.
[9] SUN Yixi, LUO Yuqin, QIAN Yeqing, DONG Minyue, JIN Fan. Single nucleotide polymorphism-array in genetic analysis of chorionic villi from early spontaneous miscarriages[J]. J Zhejiang Univ (Med Sci), 2017, 46(3): 262-267.
[10] YAN Kai, JIN Fan. Advances on prenatal diagnosis of birth defects associated with genetic disorders[J]. J Zhejiang Univ (Med Sci), 2017, 46(3): 227-232.
[11] ZHOU Qihong, YU Huijuan, FU Fengyun, YE Haipeng. Assessment of hematopoiesis and cytogenetics changes in interventional radiologists[J]. J Zhejiang Univ (Med Sci), 2016, 45(6): 626-630.
[12] LU Pei-ying, GU Wei, PANG Xiao-hong, SHAN Peng-fei. A rare case of Silver-Russell syndrome in adult and literature review[J]. J Zhejiang Univ (Med Sci), 2015, 44(3): 335-338.
[13] ZHANG Hong, GU Wei, JIA Min-yue, et al.. Progress on genetic basis of primary aldosteronism[J]. J Zhejiang Univ (Med Sci), 2014, 43(5): 612-.
[14] . Research progress on spindle assembly checkpoint gene BubR1[J]. J Zhejiang Univ (Med Sci), 2011, 40(4): 446-450.