产前诊断16p13.11微缺失/微重复胎儿的遗传学分析和妊娠结局  

Pregnancy outcomes and genetic analysis of prenatal 16p13.11microdeletion and microduplication fetuses

作　　者：罗小金 曹梦婷 刘维强 胡亮 陈晓杭 牛宏艳 丛潇怡 LUO Xiao-jin;CAO Meng-ting;LIU Wei-qiang;HU Liang;CHEN Xiao-hang;NIU Hong-yan;CONG Xiao-yi(Longgang District Maternity&Child Healthcare Hospital of Shenzhen City(Longgang Maternity and Child Institute of Shantou University Medical College),Shenzhen 518172;Department of Epidemiology,School of Public Health,Fudan University,Shanghai 200032;School of Public Health(Shenzhen),Sun Yat-sen University,Shenzhen 518106)

机构地区：[1]深圳市龙岗区妇幼保健院(汕头大学医学院龙岗妇幼临床学院),深圳518172 [2]复旦大学公共卫生学院流行病学教研室,上海200032 [3]中山大学公共卫生学院(深圳),深圳518106

出　　处：《生殖医学杂志》2023年第11期1693-1698,共6页Journal of Reproductive Medicine

基　　金：广东省医学科学技术研究基金项目(A2017359);深圳市龙岗区医疗卫生科技计划项目(LGKCYLWS2020106,LGKCYLWS2020157,LGKCYLWS2021000024)。

摘　　要：目的分析孕中晚期16p13.11微缺失/微重复胎儿的超声表现、单核苷酸多态性微阵列(SNP-array)结果、妊娠结局和随访资料,探索产前16p13.11微缺失/微重复综合征的基因组信息与临床表型的关系。方法回顾性分析2017年10月至2023年2月在深圳市龙岗区妇幼保健院经产前SNP-array诊断为16p13.11微缺失/微重复胎儿的18例孕妇的临床资料。分析这些病例的拷贝数变异(CNVs)片段最小重复区域及相关基因和超声异常情况、妊娠结局和出生后状况的关系。结果18例16p13.11微缺失/微重复胎儿中2例为微缺失,片段大小分别为1.4 Mb和2.85 Mb,均为致病性CNV;16例为微重复,片段大小为790 kb~2.8 Mb,均为临床意义不明(VOUS)。18例胎儿中17例最小重叠区域为15.5~16.3 Mb,涉及的基因主要包含MARF1、NED1、MYH11、CEP20、ABCC1等。7例(38.9%,7/18)有超声检查异常,以心血管异常为主(71.4%,5/7)。14例进行了亲本来源检测,母源遗传6例,父源遗传3例,新发变异5例。3例病例(16.7%,3/18)选择引产;15例(83.3%,15/18)选择继续妊娠直至分娩,其中1例新生儿右耳听力受损,1例新生儿室间隔缺失,其余随访均无异常。结论16p13.11微缺失/微重复胎儿超声检查表现主要为心血管异常。当胎儿SNP-array诊断为16p13.11微缺失/微重复时,应对其基因组信息与临床表型相关性进行分析,科学指导孕妇的妊娠选择。Objective:To analyze the ultrasound manifestations,single nucleotide polymorphism array(SNP array)results,pregnancy outcomes,and follow-up data of 16p13.11microdeletion/microduplication fetuses in the middle and late stages of pregnancy,and explore the relationship between genomic information and clinical phenotype of 16p13.11microdeletion/microduplication syndrome.Methods:The clinical data of 18pregnancy women diagnosed with 16p13.11 microdeletion and microduplication by prenatal SNP-array in Longgang District Maternity&Child Healthcare Hospital from October 2017to February 2023 were retrospectively analyzed.The minimum repeat regions of copy number variations(CNVs)fragments and their correlation with ultrasound abnormalities,pregnancy outcomes,and postnatal conditions in these patients were analyzed.Results:Among the 18 patients with 16p13.11 microdeletion/microduplication,2 patients had microdeletions with fragment sizes of 1.4 Mb and 2.85 Mb respectively,both of them were pathogenic CNVs.Sixteen patients had microduplications with fragment sizes ranging from 790Kb to 2.8Mb,all of them were variants of uncertain significance(VOUS).Among the 18patients,17had a minimum overlap region of 15.5 Mb to 16.3 Mb,mainly containing genes such as MARF1,NED1,MYH11,CEP20and ABCC1.Seven patients(38.9%,7/18)had ultrasound abnormalities,with cardiovascular abnormalities being the main case(71.4%,5/7).Fourteen patients underwent parental source testing,including 6 patients of maternal inheritance,3patients of paternal inheritance,and 5patients of new mutations.Three patients(16.7%,3/18)chose induced abortion.Fifteen patients(83.3%,15/18)chose to continue pregnancy until delivery,including one newborn with hearing impairment in the right ear,one newborn with ventricular septal defect,and other follow-up showed no abnormalities.Conclusions:Cardiovascular abnormalities are the mainly ultrasound manifestations of 16p13.11 microdeletion/microduplication in fetuses.When fetal is diagnosed with 16p13.11 microdeletion/microduplication

关 键 词：16p13.11微缺失/微重复 单核苷酸多态性微阵列 拷贝数变异 产前诊断 

分 类 号：R715.5[医药卫生—妇产科学]