目的:总结单基因全面性生长发育落后/智力障碍（global developmental delay/intellectual disability, GDD/ID）家系的产前诊断特点。方法:回顾性分析2015年1月至2019年6月就诊于北京大学第一医院遗传咨询门诊的43个单基因GDD/ID家系的产前分子诊断结果。所有产前诊断结果在妊娠结束后进行子代致病变异位点验证，随访妊娠结局和子代健康状况。采用描述性统计分析。结果:在43个家系中常染色体隐性遗传的GDD/ID家系24个，检测到胎儿携带2个致病变异（患胎）有6例（25%），携带1个致病变异（携带者）13例（55%），5例（20%）未携带变异。常染色体显性遗传家系13个，其中11例胎儿不携带变异，2例胎儿携带与先证者相同的变异（患胎），但仅在其中1个家系中检测到父亲外周血存在低丰度变异，另1个家系父母外周血未检出变异，故推测2例患胎的变异来自亲代生殖嵌合。X连锁遗传家系6个，1例胎儿为携带致病变异的男性（患胎），其余5例胎儿不携带变异。产前标本均经连锁分析以排除母源污染。妊娠结束后子代标本验证结果与产前诊断一致。9例患胎均引产终止妊娠，余34例胎儿已出生，且健康状况好。结论:对于单基因GDD/ID家系，产前分子诊断可在早、中孕期诊断胎儿是否携带变异。对于新生变异致病的常染色体显性和X连锁遗传家系，需警惕隐匿的亲代嵌合情况，故也建议进行产前诊断。“,”Objective:To summarize the prenatal diagnostic characteristics of monogenic global developmental delay/intellectual disability(GDD/ID) pedigrees.Methods:This study retrospectively collected the prenatal molecular diagnostic results of 43 pedigrees that were affected with monogenic GDD/ID in the genetic counseling clinic of Peking University First Hospital from January 2015 to June 2019. The results of prenatal molecular tests were validated after birth or pregnancy termination. Pregnancy outcomes and healthy condition of the offspring were followed up. All data were analyzed by descriptive statistical analysis.Results:Among the 43 pedigrees, 24 were affected with autosomal recessive inheritance (AR) GDD/ID, in which six (25%) fetuses were found to carry two pathogenic variants; 13 (55%) had only one pathogenic variant; five (20%) did not harbor any variant. GDD/ID inherited in an autosomal dominant inheritance (AD) pattern was found in 13 pedigrees, in which 11 fetuses carried no variants while the other two fetuses had the same variants as the proband had (in one pedigree, a low-level variant was detected in the peripheral blood sample of the father while absent in peripheral blood samples of parents in the other pedigree, so it was suspected that the variants of these two affected fetuses were inherited from parental mosaicism). In the other six pedigrees with X-linked inheritance (XL) of GDD/ID, one male fetus was found to harbor the pathogenic variant, while no variants were detected in the others. Maternal contamination was excluded in all prenatal samples using short tandem repeat for linkage analysis. Postnatal validations were consistent with the prenatal tests. All nine affected fetuses were terminated, and the other thirty-four children were delivered and in good health.Conclusions:Prenatal molecular diagnostic test is an effective method to detect pathogenic variants during the first and second trimesters for pedigrees affected by monogenic GDD/ID. For pedigrees affected with AD or XL patterns caused by n de novo mutations, potential parental mosaicism should be noted and prenatal diagnostic tests are also recommended.n