染色体微阵列分析技术在2600例流产物中的应用

doi:10.16288/j.yczz.18-120

遗传 ›› 2018, Vol. 40 ›› Issue (9): 779-788.doi: 10.16288/j.yczz.18-120

染色体微阵列分析技术在2600例流产物中的应用

彭继苹¹(),袁海明²

^1. 北京金域医学检验实验室有限公司,北京 100010
^2. 广州金域医学检验中心有限公司,广州 510330

收稿日期:2018-06-29 修回日期:2018-08-03 出版日期:2018-09-20 发布日期:2018-08-03
作者简介:彭继苹,硕士研究生,研究方向：分子遗传学。E-mail: pengjiping0419@163.com

Application of chromosomal microarray analysis for a cohort of 2600 Chinese patients with miscarriage

Peng Jiping¹(),Yuan Haiming²

^1. Beijing Kingmed Center for Clinical Laboratory, Beijing 100010, China
^2. Guangzhou Kingmed Center for Clinical Laboratory, Guangzhou510330, China

Received:2018-06-29 Revised:2018-08-03 Online:2018-09-20 Published:2018-08-03

摘要/Abstract

摘要：

染色体微阵列分析(chromosomal microarray analysis, CMA)是一种通过对染色体进行全基因组扫描来筛查染色体数目和结构异常的检测技术,是儿科和产前遗传诊断的常规工具,已被应用于流产病因分析。本研究应用CMA技术在全基因组水平分析引起流产的染色体异常情况,并评估该技术在临床流产中的应用价值。对收集的2600例流产样本进行CMA技术检测,成功检测了2505例,成功率高达96.3%,其中1021例用CytoScan Optima芯片进行检测,1211例用CytoScan 750K芯片进行检测,273例用CytoScan HD芯片进行检测。利用这3种芯片共检出967例(38.60%)样本发生染色体异常,其中通过CytoScan Optima芯片检出506例(50.00%),CytoScan 750K芯片检出388例(32.00%),CytoScan HD芯片检出73例(26.74%)。在967例染色体异常中,有801例(82.83%)发生染色体数目异常,94例(9.72%)发生染色体结构异常,56例(5.79%)发生嵌合体,16例(1.65%)检出纯合区域。本研究结果表明,CMA可应用于临床流产物的遗传学诊断,是一种可靠、稳定、高分辨的技术,其检测结果能够对再生育风险评估提供指导。

关键词: 流产, 染色体微阵列分析, 染色体数目异常, 染色体结构异常, 嵌合体, 染色体纯合区域

Abstract:

Chromosomal microarray analysis (CMA) is a technique for screening numerical and structural abnormalities of chromosomes at the whole genome level. It is a routine tool for pediatric and prenatal genetic diagnoses. It has also been applied to investigate the genetic etiologies of miscarriages. In our study, we used the CMA technology to analyze the chromosomal variations of fetuses from miscarriages at the whole genome level, and to evaluate its clinical applications in studies of miscarriages. The CMA analyses were performed on 2600 miscarriage specimens, of which 2505 specimens (96.35%) were successfully analyzed. Among them, 1021 specimens were analyzed with CytoScan Optima chip; 1211 specimens were analyzed with CytoScan 750K chip; and 273 cases were analyzed with CytoScan HD chip. Chromosomal abnormalities were identified in 967 specimens (38.6%) by these 3 kinds of chips, of which 506 specimens (50.00%) were detected with CytoScan Optima chip; 388 specimens were detected by CytoScan 750K chip (32.00%); and 73 cases (26.74%) were detected in CytoScan HD chip. Among the 967 cases of chromosomal abnormalities, 801 cases (82.83%) were numerical chromosomal abnormalities; 94 cases (9.72%) were structural abnormalities; 56 cases (5.79%) were mosaicisms; and 16 (1.65%) were regions of homozygosity. Our research suggests that CMA is a reliable, robust, and high-resolution technology for genetic diagnosis of miscarriage in clinical practice, which can also provide results as guidance for the risk assessment of assisted fertility.

Key words: miscarriage, chromosomal microarray analysis, numerical chromosomal abnormalities, structural chromosomal abnormalities, mosaicism, regions of homozygosity

彭继苹, 袁海明. 染色体微阵列分析技术在2600例流产物中的应用[J]. 遗传, 2018, 40(9): 779-788.

Peng Jiping, Yuan Haiming. Application of chromosomal microarray analysis for a cohort of 2600 Chinese patients with miscarriage[J]. Hereditas(Beijing), 2018, 40(9): 779-788.

参考文献

[1]	Muttukrishna S, Jauniaux E, Greenwold N, McGarrigle H, Jivraj S, Carter S, Elgaddal S, Groome N, Regan L . Circulating levels of inhibin A, activin A and follistatin in missed and recurrent miscarriages. Hum Reprod, 2002,17(12):3072-3078.
[2]	van den Berg MM, van Maarle MC, van Wely M, Goddijn M . Genetics of early miscarriage. Biochim Biophys Acta, 2012,1822(12):1951-1959.
[3]	Rai R, Regan L . Recurrent miscarriage. Lancet, 2006,368(9535):601-611.
[4]	Goddijn M, Leschot NJ . Genetic aspects of miscarriage. Baillieres Best Pract Res Clin Obstet Gynaecol, 2000,14(5):855-865.
[5]	Meng JL . Application of chromosome microarray analysis in the diagnosis of prenatal genetic diseases. Prog Obstetr Gynecol, 2015,24(5):390-393.
[5]	孟金来 . 染色体微阵列分析技术在产前遗传性疾病诊断中的应用进展. 现代妇产科进展, 2015,24(5):390-393.
[6]	Wang Y, Cheng Q, Meng L, Luo C, Hu H, Zhang J, Cheng J, Xu T, Jiang T, Liang D, Hu P, Xu Z . Clinical application of SNP array analysis in first-trimester pregnancy loss: a prospective study. Clin Genet, 2017,91(6):849-858.
[7]	Shearer BM, Thorland EC, Carlson AW, Jalal SM, Ketterling RP . Reflex fluorescent in situ hybridization testing for unsuccessful product of conception cultures: a retrospective analysis of 5555 samples attempted by conventional cytogenetics and fluorescent in situ hybridization. Genet Med, 2011,13(6):545-552.
[8]	Haoud K, Mellali S, Gouas L, Tchirkov A, Vago P, Moulessehoul S . Prevalence of aneuploidies in products of spontaneous abortion: interest of FISH and MLPA. Morphologie, 2014,98(320):40-46.
[9]	Warren JE, Turok DK, Maxwell TM, Brothman AR, Silver RM . Array comparative genomic hybridization for genetic evaluation of fetal loss between 10 and 20 weeks of gestation. Obstet Gynecol, 2009,114(5):1093-1102.
[10]	Dhillon RK, Hillman SC, Morris RK, McMullan D, Williams D, Coomarasamy A, Kilby MD . Additional information from chromosomal microarray analysis (CMA) over conventional karyotyping when diagnosing chromosomal abnormalities in miscarriage: a systematic review and meta-analysis. BJOG, 2014,121(1):11-21.
[11]	Reddy UM, Page GP, Saade GR, Silver RM, Thorsten VR, Parker CB, Pinar H, Willinger M, Stoll BJ, Heim-Hall J, Varner MW, Goldenberg RL, Bukowski R, Wapner RJ, Drews-Botsch CD, O'Brien BM, Dudley DJ, Levy B, NICHD Stillbirth Collaborative Research Network . Karyotype versus microarray testing for genetic abnormalities after stillbirth. N Engl J Med, 2012,367(23):2185-2193.
[12]	Gao J, Liu C, Yao F, Hao N, Zhou J, Zhou Q, Zhang L, Liu X, Bian X, Liu J . Array-based comparative genomic hybridization is more informative than conventional karyotyping and fluorescence in situ hybridization in the analysis of first-trimester spontaneous abortion. Mol Cytogenet, 2012,5(1):33.
[13]	Kearney HM, Thorland EC, Brown KK, Quintero-Rivera F, South ST , Working Group of the American College of Medical Genetics Laboratory Quality Assurance Committee. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genet Med, 2011,13(7):680-685.
[14]	Brady PD, Vermeesch JR . Genomic microarrays: a technology overview. Prenat Diagn, 2012,32(4):336-343.
[15]	Breman A, Pursley AN, Hixson P, Bi W, Ward P, Bacino CA, Shaw C, Lupski JR, Beaudet A, Patel A, Cheung SW, Van den Veyver I . Prenatal chromosomal microarray analysis in a diagnostic laboratory; experience with >1000 cases and review of the literature. Prenat Diagn, 2012,32(4):351-361.
[16]	Robberecht C, Schuddinck V, Fryns JP, Vermeesch JR . Diagnosis of miscarriages by molecular karyotyping: benefits and pitfalls. Genet Med, 2009,11(9):646-654.
[17]	Choy KW, Setlur SR, Lee C, Lau TK . The impact of human copy number variation on a new era of genetic testing. BJOG, 2010,117(4):391-398.
[18]	Lee CN, Lin SY, Lin CH, Shih JC, Lin TH, Su YN . Clinical utility of array comparative genomic hybridisation for prenatal diagnosis: a cohort study of 3171 pregnancies. BJOG, 2012,119(5):614-625.
[19]	Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, Church DM, Crolla JA, Eichler EE, Epstein CJ, Faucett WA, Feuk L, Friedman JM, Hamosh A, Jackson L, Kaminsky EB, Kok K, Krantz ID, Kuhn RM, Lee C, Ostell JM, Rosenberg C, Scherer SW, Spinner NB, Stavropoulos DJ, Tepperberg JH, Thorland EC, Vermeesch JR, Waggoner DJ, Watson MS, Martin CL, Ledbetter DH . Consensus statement: chromosomal microarray is a first- tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet, 2010,86(5):749-764.
[20]	McNamee K, Dawood F, Farquharson RG . Evaluation of array comparative genomic hybridization in recurrent miscarriage. Br J Hosp Med (Lond), 2013,74(1):36-40.
[21]	Philipp T, Philipp K, Reiner A, Beer F, Kalousek DK . Embryoscopic and cytogenetic analysis of 233 missed abortions: factors involved in the pathogenesis of developmental defects of early failed pregnancies. Hum Reprod, 2003,18(8):1724-1732.
[22]	Yuan HM, Chen MF, Deng XY, Lv fen . Application of chromosomal microarray analysis for a cohort of Chinese patients with spontaneous miscarriage. Chin J Med Genet, 2016,33(34):442-446.
[22]	袁海明, 陈梦帆, 邓小燕, 吕芬 . 染色体微阵列技术在自然流产病因诊断中的应用. 中华医学遗传学杂志, 2016,33(4):442-446.
[23]	Fritz B, Hallermann C, Olert J, Fuchs B, Bruns M, Aslan M, Schmidt S, Coerdt W, Müntefering H, Rehder H . Cytogenetic analyses of culture failures by comparative genomic hybridisation (CGH)-Re-evaluation of chromosome aberration rates in early spontaneous abortions. Eur J Hum Genet, 2001,9(7):539-547.
[24]	Menasha J, Levy B, Hirschhorn K, Kardon NB . Incidence and spectrum of chromosome abnormalities in spontaneous abortions: new insights from a 12-year study. Genet Med, 2005,7(4):251-263.
[25]	Sugiura-Ogasawara M, Ozaki Y, Katano K, Suzumori N, Kitaori T, Mizutani E . Abnormal embryonic karyotype is the most frequent cause of recurrent miscarriage. Hum Reprod, 2012,27(8):2297-2303.
[26]	Ko DS, Cho JW, Lee HS, Kim JY, Kang IS, Yang KM, Lim CK . Preimplantation genetic diagnosis outcomes and meiotic segregation analysis of robertsonian translocation carriers. Fertil Steril, 2013,99(5):1369-1376.
[27]	ACOG Committee on Practice Bulletins. ACOG Practice Bulletin No. 77: screening for fetal chromosomal abnormalities. Obstet Gynecol, 2007,109(1):217-227.
[28]	Sugiura-Ogasawara M, Ozaki Y, Sato T, Suzumori N, Suzumori K . Poor prognosis of recurrent aborters with either maternal or paternal reciprocal translocations. Fertil Steril, 2004,81(2):367-373.
[29]	Suzumori N, Sugiura-Ogasawara M . Genetic factors as a cause of miscarriage. Curr Med Chem, 2010,17(29):3431-3437.
[30]	Levy B, Sigurjonsson S, Pettersen B, Maisenbacher MK, Hall MP, Demko Z, Lathi RB, Tao R, Aggarwal V, Rabinowitz M . Genomic imbalance in products of conception: single-nucleotide polymorphism chromosomal microarray analysis. Obstet Gynecol, 2014,124(2 Pt 1):202-209.
[31]	Sahoo T, Dzidic N, Strecker MN, Commander S, Travis MK, Doherty C, Tyson RW, Mendoza AE, Stephenson M, Dise CA, Benito CW, Ziadie MS, Hovanes K . Comprehensive genetic analysis of pregnancy loss by chromosomal microarrays: outcomes, benefits, and challenges. Genet Med, 2017,19(1):83-89.
[32]	Delio M, Guo T, McDonald-McGinn DM, Zackai E, Herman S, Kaminetzky M, Higgins AM, Coleman K, Chow C, Jalbrzikowski M, Bearden CE, Bailey A, Vangkilde A, Olsen L, Olesen C, Skovby F, Werge TM, Templin L, Busa T, Philip N, Swillen A, Vermeesch JR, Devriendt K, Schneider M, Dahoun S, Eliez S, Schoch K, Hooper SR, Shashi V, Samanich J, Marion R, van Amelsvoort T, Boot E, Klaassen P, Duijff SN, Vorstman J, Yuen T, Silversides C, Chow E, Bassett A, Frisch A, Weizman A, Gothelf D, Niarchou M, van den Bree M, Owen MJ, Su?er DH, Andreo JR, Armando M, Vicari S, Digilio MC, Auton A, Kates WR, Wang T, Shprintzen RJ, Emanuel BS, Morrow BE . Enhanced maternal origin of the 22q11.2 deletion in velocardiofacial and DiGeorge syndromes. Am J Hum Genet, 2013,92(3):439-447.
[33]	Rosenfeld JA, Tucker ME, Escobar LF, Neill NJ, Torchia BS, McDaniel LD, Schultz RA, Chong K, Chitayat D . Diagnostic utility of microarray testing in pregnancy loss. Ultrasound Obstet Gynecol, 2015,46(4):478-486.
[34]	Goodship J, Cross I, LiLing J, Wren C . A population study of chromosome 22q11 deletions in infancy. Arch Dis Child, 1998,79(4):348-351.
[35]	Merla G, Brunetti-Pierri N, Micale L, Fusco C . Copy number variants at Williams-Beuren syndrome 7q11.23 region. Hum Genet, 2010,128(1):3-26.
[36]	Str?mme P, Bj?rnstad PG, Ramstad K . Prevalence estimation of Williams syndrome. J Child Neurol, 2002,17(4):269-271.
[37]	Gong X, Jiang YW, Zhang X, An Y, Zhang J, Wu Y, Wang J, Sun Y, Liu Y, Gao X, Shen Y, Wu X, Qiu Z, Jin L, Wu BL, Wang H . High proportion of 22q13 deletions and SHANK3 mutations in Chinese patients with intellectual disability. PLoS One, 2012,7(4):e34739.
[38]	Gogiel M, Begemann M, Spengler S, Soellner L, G?retzlehner U, Eggermann T, Strobl-Wildemann G . Genome-wide paternal uniparental disomy mosaicism in a woman with Beckwith-Wiedemann syndrome and ovarian steroid cell tumour. Eur J Hum Genet, 2013,21(7):788-791.
[39]	Inbar-Feigenberg M, Choufani S, Cytrynbaum C, Chen YA, Steele L, Shuman C, Ray PN, Weksberg R . Mosaicism for genome-wide paternal uniparental disomy with features of multiple imprinting disorders: diagnostic and management issues. Am J Med Genet A, 2013,161A(1):13-20.
[40]	Kearney HM, Kearney JB, Conlin LK . Diagnostic implications of excessive homozygosity detected by SNP- based microarrays: consanguinity, uniparental disomy, recessive single-gene mutations. Clin Lab Med, 2011, 31(4): 595-613, ix.

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

染色体微阵列分析技术在2600例流产物中的应用

Application of chromosomal microarray analysis for a cohort of 2600 Chinese patients with miscarriage

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

[1]	梁小妍，刘学庆，丁裕斌，陈雪梅，王应雄，何俊琳. 难免流产蜕膜组织遗传印记基因PEG10的表达[J]. 遗传, 2008, 30(6): 735-740.
[2]	钱卫平，谭玉梅，谭跃球，宋丹，许晓清，李麓芸，卢光琇. 应用端粒区带涂染探针检测染色体微小结构重排[J]. 遗传, 2006, 28(5): 518-520.
[3]	周波，唐艳平，刘永章. 一例特殊inv(Y)形成机理的研究[J]. 遗传, 2006, 28(2): 148-152.
[4]	栗茂腾，余龙江，王丽梅，刘建民，雷呈. 菊花花色遗传及花色嵌合体发现[J]. 遗传, 2005, 27(6): 948-952.
[5]	韩维田，王格，姜淼，张志芬，刘广兴，王朝祥，边超英，于平. 16种罕见的人类染色体异常核型报告[J]. 遗传, 2005, 27(2): 201-204.
[6]	刘永章，帅茨霞，董杰影. 用间期荧光原位杂交检测卵巢癌细胞中X染色体数目的异常[J]. 遗传, 2005, 27(2): 185-189.
[7]	燕海峰，肖兵南，P TREFIL，郭湘霞，吴晓林. 鸡囊胚细胞嵌合体制作技术研究及其应用前景[J]. 遗传, 2004, 26(4): 537-543.
[8]	刘京昇，李效良，魏成芳，赵静，李新华，宗传龙，杜可明，李桂信，郭淼. 染色体着丝点结构变化与习惯性流产的关系[J]. 遗传, 2003, 25(4): 393-395.
[9]	付建华，李露霞，付睿婷，秦冬梅. 习惯性流产伴罕见Rob(13;21)的异常核型分析[J]. 遗传, 2003, 25(2): 145-145.
[10]	黎刚，王应雄，刘学庆，翁亚光，何俊琳，陈雪梅. 原因不明性习惯性流产患者子宫蜕膜白血病抑制因子基因表达研究[J]. 遗传, 2002, 24(3): 251-253.
[11]	燕海峰，PTrefil，肖兵南，吴晓林. 特异性PCR反应鉴别携带W染色体的嵌合体公鸡子代性别的研究[J]. 遗传, 2001, 23(4): 306-308.
[12]	王应雄，何俊琳，翁亚光，刘学庆，陈雪梅，杨戎，魏莎莉，刘孝云. 习惯性流产胚胎绒毛细胞LIF基因的表达[J]. 遗传, 2001, 23(2): 111-113.
[13]	侯南英，杨建华. 一例t(2；14)致自然流产报告[J]. 遗传, 2000, 22(5): 292-292.
[14]	李永全，郑克勤，周汝滨，潘超仁，廖霞，陈小萍. 9种新的人类染色体异常核型报告[J]. 遗传, 1999, 21(3): 13-720.
[15]	李永全，潘超仁，周汝滨，郑克勤，廖霞，陈小萍，陈犇. 新近发现的自然流产夫妇的几种染色体异常[J]. 遗传, 1995, 17(6): 24-26.