产前遗传学诊断拷贝数变异和纯合区域的数据分析解读及报告规范化共识

A consensus recommendation for the interpretation and reporting of copy number variation and regions of homozygosity in prenatal genetic diagnosis

由致病性基因组拷贝数变异(pathogenic copy number variation,pCNV)导致的染色体微缺失、微重复综合征是胎儿出生缺陷的一个重要遗传学病因。近年来随着染色体微阵列分析(chromosomal microarray analysis,CMA)和基于二代测序(next generation sequencing,NGS)的基因组拷贝数变异测序技术(copy number variation sequencing,CNV-seq)在产前诊断领域广泛应用,规范CNV分析流程和报告的重要性日益彰显。同时,对基因组纯合区域(regions of homozygosity,ROH)的分析和报告流程国内也亟需专业的指导意见。基于此,本组专家就CNV、ROH的数据分析流程、报告标准及报告内容等达成共识,以期规范CMA/CNV-seq等技术在产前诊断中的应用。

Chromosomal microdeletions and microduplications have been proven to be a significant proportion of genetic factors underlying birth defects.Chromosomal microarray analysis(CMA)and next generation sequencing-based copy number variation(CNV-seq)assay have been recommended as first-tier tests for prenatal evaluation of disease-causing CNV across the genome.With the broad application of such technologies in prenatal genetic diagnosis,there is a needed to enhance the consistency in interpretation and reporting of CNV results in clinical laboratories across China.In addition,a standard guideline for prenatal analysis and reporting of regions of homozygosity(ROH)is also required.To assist the classification,interpretation and reporting of CNV/ROH,the following recommendations have been developed,which may enhance a standard application of CMA/CNV-seq techniques in prenatal genetic diagnosis.