摘要
目的对早、中孕期自然流产组织标本进行基于单核苷酸多态性(single nucleotide polymorphism,SNP)探针的染色体微阵列分析(chromosomal microarray analysis,CMA),在更深层次基因组水平探讨与流产可能相关的遗传学原因。方法回顾性分析本院961例孕20周前孕妇自然流产标本的CMA检测结果。结果(1)流产标本染色体总异常率为54.44%(515/946),包括单条染色体异常39.53%、两条染色体异常2.22%、多染色体异常0.42%、三倍体及超、亚三倍体4.86%、拷贝数异常(copy number variants,CNV)4.33%、纯合区域(regions of homozygosity,ROH)0.74%、嵌合体2.22%及异源性嵌合(chimera)0.11%;(2)对41例CNV分析,致病及可能致病性CNV达85.36%,检出临床意义不确定CNV12.20%和可能良性CNV2.44%;(3)7例ROH中2例为全基因组纯合,2例为16号染色体短臂末端大片段纯合,1例为整个21号染色体完全纯合,提示单亲二体可能。结论染色体异常是导致流产的重要因素,应用含SNP探针的CMA技术可以额外增加异常检出率,更好地为自然流产患者在再次妊娠前进行生育风险评估并提供指导。
Objective To explore possible genetic causes associated with early pregnancy loss using chromosomal microarray analysis(CMA)with single nucleotide polymorphism(SNP)probes.Methods A retrospective review was performed by the CMA of samples from 961 patients who spontaneously aborted in our hospital before the 20th week of pregnancy.Results(1)The total chromosome abnormality rate in miscarriage samples was 54.44%(515/946),including single chromosome abnormality(39.53%),two chromosome abnormality(2.22%),multi-chromosome abnormality(0.42%),triploidy or hypertriploidy(4.86%),copy number variants(CNVs)in 41 cases(4.33%),regions of homozygosity(ROH,0.74%),mosaic(2.22%)and chimera(0.11%).(2)CNV analysis of 41 cases showed that 85.36%were pathogenic and likely pathogenic,12.20%were classified as clinical significance unknown and 2.44%were interpreted as likely benign;(3)Among the cases of ROH,2 cases shown whole-genome homozygosity and 1 case had completely homozygous at chromosome 21.The homozygous regions in 2 cases were located at the end of the short arm of chromosome 16,suggesting the mechanism of ROH in such cases could be the result of isodisomy.Conclusion Chromosome abnormality is an important genetic factor causing pregnancy loss.The application of CMA with SNP probes can indeed improve the detection rate of chromosome abnormalities and evaluate the risk of reproductive fertility in patients with pregnancy loss.
作者
朱丽芬
张慧敏
杜绮婷
孙筱放
刘维强
Zhu Lifen;Zhang Huimin;Du Qiting;Sun Xiaofang;Liu Weiqiang(Department of Obstetrics and Gynecology,Guangdong Province Key Laboratory of Major Obstetric Diseases,The Third Affiliated Hospital of Guangzhou Medical University,Guangzhou,Guangdong 510150,China;Central Laboratory,Shenzhen Longgang District Maternity and Child Healthcare Hospital of Shenzhen City,Shenzhen,Guangdong 518172,China;Department of Prenatal Diagnostic Center,Third Affiliated Hospital of Guangzhou Medical University,Guangzhou,Guangdong 510150,China)
出处
《中华医学遗传学杂志》
CAS
CSCD
2022年第6期576-580,共5页
Chinese Journal of Medical Genetics
基金
广东省自然科学基金(2019A1515011302)。
