摘要目的 应用单核苷酸多态性微阵列芯片(single nucleotide polymorphism array,SNP array)检测平台对超声发现的各系统畸形胎儿及孕妇不良生育史者进行产前诊断,探讨胎儿畸形及不良生育史与拷贝数变异(copy number variations,CNVs)的病因学关系,及时干预并预防出生缺陷患儿的出生.方法收集2013年1月至2014年12月在湖南省妇幼保健院就诊的超声异常(室间隔缺损、房间隔缺损、法洛氏四联症、侧脑室增宽、胎儿宫内发育迟缓、颈部透明层增厚、鼻骨长度异常)及孕妇不良生育史胎儿的样本共314例(其中羊水样本189例、脐带血样本125例),排除G显带技术染色体水平可见的畸变后,进一步行SNP array分型检测,对检出的CNVs进行基因型与表型关系分析,查询相关文献后探讨其致病性.结果 SNP array检测发现28例样本存在阳性CNVs (8.91％,28/314),其中11例重复型CNVs,9例缺失型CNVs,4例杂合性丢失,4例缺失合并重复型CNVs.重复片段大小在0.47～16.7 Mb之间,缺失片段在0.16～13.3 Mb之间.结合相关数据库及文献比对,15例为已知的微缺失/微重复综合征或其累及范围与临床表型的拷贝数畸变,余13例为良性或临床意义未明的CNVs.结论 本研究中通过SNP array高通量平台,在常规G显带染色体检查未见异常的胎儿样本中发现4.78％(15/314)存在亚显微结构的致病性畸变,53％(8/15)为已知的综合征或其区域内的畸变,其余47％为非综合征区域内畸变.在产前诊断中,引入SNP array平台有利于发现更多未知的综合征型疾病,为遗传病诊断及咨询提供依据.

abstractsObjective To apply single nucleotide polymorphism microarray (SNP array) for the detection of genome-wide copy number variations(CNVs) in fetuses with malformations and women with an adverse reproductive history,and to explore the correlation of rare CNVs with the clinical manifestations.Methods Amniotic fluid and umbilical cord blood samples were collected from 314 women with singleton pregnancy.SNP array was performed on samples where chromosomal abnormalities were excluded after Gbanding analysis.Results Pathological CNVs were detected in 8.91％ (28/314) of all samples,which included 11 duplications,9 deletions,4 loss of heterozygosity (LOH),and 4 conjoined deletions and duplications.The sizes of duplications and deletions were between 0.47 Mb and 16.7 Mb,and between 0.16 Mb and 13.3 Mb,respectively.Fifteen CNVs were mapped to the regions of microdeletion or microduplication syndromes or regions associated with clinical manifestations,while the remainder 13 were considered benign or variant of uncertain significance.Conclusion A proportion of fetuses with malformations and women with an adverse reproductive history may be attributed to CNVs,half of which are mapped with to the regions of well known syndromes.SNP array may facilitate discovery of new syndromes and provide a basis for genetic counseling and prenatal diagnosis.