摘要
目的 应用染色体微阵列分析技术（chromosomal microarray analysis,CMA）在全基因组水平分析颈项透明层（nuchal translucency,NT）增厚胎儿的遗传学病因.方法 选取78位孕妇早孕期（11＋0～13＋6孕周）NT厚度≥3.0mm且标准G显带染色体核型分析正常的胎儿样本,首先提取基因组DNA,严格按照美国Affymetrix CytoScanTM HD芯片的标准操作流程进行CMA检测,并应用CHAS软件和相关生物信息学数据库对结果进行分析.CMA检测所得拷贝数变异（copy number variations,CNVs）结果进一步行实时荧光定量PCR验证.结果 CMA在6例胎儿中检出致病性CNVs（7.69％）,所检出致病性CNVs片段大小范围为0.41～15.87Mb,其中包含3种已知的微缺失/微重复综合征,分别为：Wolf-Hirschhom综合征、22q11微缺失综合征和ATR-16综合征.中孕期超声结构异常胎儿病例组和无结构异常胎儿病例组致病性CNVs的检出率分别为18.18％（2/11）和5.97％（4/67）（P=0.198,Fisher＆#39;s检验）;致病性CNVs胎儿病例组与非致病性CNVs胎儿病例组NT值的平均数分别是4.48mm和4.22 mm （P=0.735,Mann-Whitney检验）.结论 在NT增厚胎儿中,染色体微阵列分析能检测传统核型分析无法识别的染色体微缺失/微重复,对临床产前诊断及遗传咨询具有重要价值,可将疾病诊断率额外提高7.69％.
Objective To explore the genetic etiology for fetuses with increased nuchal translucency （NT） but a normal karyotype at whole genome level by chromosome microarray analysis （CMA）.Methods Seventy-eight fetuses with increased NT（≥ 3.0 mm） but a normal karyotype were collected between 11＋0 and 13＋6 gestational weeks.Genomic DNA was extracted,and microarray testing was performed using Affymetrix CytoScanTM HD arrays.The data was analyzed by CHAS software.All detected copy number variations （CNVs） were confirmed with real-time quantitative polymerase chain reaction.Results The CMA assay has detected pathogenic CNVs in 6 fetuses （7.69%）,which have ranged from 0.41 Mb to 15.87 Mb.Well-known microdeletion or microduplication syndromes including Wolf-Hirschhorn syndrome,22q11 microdeletion syndrome and ATR-16 syndrome were identified in three cases.The detection rates in fetuses with or without structural abnormalities were 18.18% and 5.97%,respectively （P=0.198 with Fisher＇s Exact Test）.The average NT in fetuses with pathogenic CNVs and non-pathogenic CNVs has measured 4.48 mm and 4.22 mm （P=0.735 by Mann-Whitney Test）.Conclusion For fetuses with increased NT,CMA can identify chromosomal microdeletion/microduplication unrecognizable by conventional karyotyping analysis.It may therefore play an important role in prenatal diagnosis and genetic counseling by improving the diagnostic rate.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2015年第3期370-374,共5页
Chinese Journal of Medical Genetics
基金
广州市科技局民生重大项目（201300000086）
广州市卫生局重点项目（201102A212026）
东莞市医学重点项目（2012105102003）.
关键词
颈项透明层增厚
染色体微阵列分析
微缺失
微重复
Increased nuchal translucency
Chromosomal microarray analysis
Microdeletion
Microduplication
作者简介
通信作者：廖灿。Email：canliao@hotmail．com
