摘要
目的:探讨Xp22.3微缺失/微重复的基因型与临床表型的相关性。方法:对15例SNP-array检测结果为Xp22.3微缺失/微重复病例的分子遗传学特征、临床表型和随访信息进行回顾性分析。结果:15例Xp22.3微缺失/微重复胎儿中,8例为微缺失病例(8/15),片段大小165~5.1Mb,片段内基因包括SHOX、ARSE、STS、ANOS1、NLGN4X、GPR143等30个OMIM基因,其中SHOX、ARSE、STS、ANOS1为单倍剂量不足基因。7例(7/15)为微重复病例,片段大小为229~1.7Mb,片段内基因包括SHOX、ARSE、ANOS1、STS、NLGN4X、GPR143等23个OMIM编码基因,不含三倍剂量敏感基因。8例微缺失病例中7例诊断为致病性拷贝数变异(CNV),1例诊断为临床意义不明(VOUS);7例微重复病例均诊断为VOUS。15例胎儿中7例(7/15)超声发现异常特征,其中四肢短小3例(3/7),唇腭裂1例(1/7),心血管异常1例(1/7),侧脑室增宽1例(1/7),鼻骨缺如1例(1/7)。对12例病例进行了亲本来源验证,5例(5/12)为母源性遗传,3例为父源性遗传(3/12)。15病例中4例(4/15)微缺失选择终止妊娠,1例稽留流产,均为男性胎儿;10例(10/15)选择继续妊娠,除1例新生儿左耳听力受损外,其余随访均无异常。结论:Xp22.3微缺失因涉及SHOX、ARSE、STS、ANOS1等单倍剂量敏感基因,为致病性CNV,表现为生长发育迟缓、软骨发育不全等症状。Xp22.3微重复无三倍剂量敏感基因,定义为VOUS,胎儿妊娠结局良好。当SNP-array诊断为Xp22.3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,为孕妇提供指导。
Objective:To explore the correlation between the genotype of Xp22.3 microdeletion/microduplication of fetuses and their clinical phenotype.Methods:A retrospective study was conducted on the molecular genetic characteristics,the clinical phenotype,and the follow-up information of 15 fetuses with Xp22.3 microdeletion/microduplication based on results of their SNP-array detection.Results:Among the 15 fetuses,there were 8 cases with Xp22.3 microdeletion,with the fragment sizes ranging from 165Kb to 5.1Mb.The genes in the fragment sizes included 30 OMIM genes,such as SHOX,ARSE,STS,ANOS1,NLGN48/15X and GPR143,and among which,the genes of SHOX,ARSE,STS,and ANOS1 were the single dose deficient genes.There were 7 cases with Xp22.3 microduplication,with the fragment sizes ranging from 229Kb to 1.7Mb.The genes in the fragment sizes included 23 OMIM coding genes,such as SHOX,ARSE,ANOS1,STS,NLGN4X and GPR143.and among which,the genes had no triple dose sensitive genes.Among 8 fetuses with microdeletion,7 cases were diagnosed as the pathogenic copy number variant(CNV),and 1was diagnosed as the variables of unknown significance(VOUS).7fetuses with microduplication were diagnosed as VOUS.Among 15fetuses with Xp22.3microdeletion/microduplication,there were 7cases with abnormal features detected by ultrasound,including 3cases with abnormal skeletal development(short limbs),1case with cleft lip and palate,1case with cardiovascular abnormalities,1case with widened lateral ventricle and 1case with the nasal bone absent.Parent source verification was conducted on 14fetuses,including 5cases from maternal inheritance and 3cases from paternal inheritance.Among 15fetuses with Xp22.3 microdeletion/microduplication,4cases with microdeletion had chosen to terminate pregnancy and 1case had missed miscarriage,and all of which were male fetuses.Among 15fetuses with Xp22.3 microdeletion/microduplication,10cases had chosen to continue pregnancy,and except 1newborn with hearing loss in the right left ear,and the other newborn showed no abnormaliti
作者
李双武
周飞
丛潇怡
姚瑶
罗小金
刘维强
LI Shuangwu;ZHOU Fei;CONG Xiaoyi;YAO Yao;LUO Xiaojin;LIU Weiqiang(Longgang District Maternity and Child Health Care Hospital of Shenzhen(Longgang Maternity and Child Institute o f Shantou University Medical College),Shenzhen,Guangdong Province,518172)
出处
《中国计划生育学杂志》
2024年第3期713-717,共5页
Chinese Journal of Family Planning
基金
广东省自然科学基金(2022A1515011605)
深圳市龙岗区医疗卫生科技计划项目(LGKCYLWS2020106)(LGKCYLWS2021000024)
龙岗区出生缺陷预防重点实验室(LGKCZSYS2018000010)。
