七例16p12.2微缺失或微重复胎儿的产前诊断和遗传学分析  

Prenatal diagnosis and genetic analysis of seven fetuses with 16p12.2 microdeletion or microduplication

作　　者：毛雅珍 林元波 林雨虹 刘欣茹 黄秀琼 Mao Yazhen;Lin Yuanbo;Lin Yuhong;Liu Xinru;Huang Xiuqiong(Department of Clinical Laboratory,the First Affiliated Hospital of Fujian Medical University,Fuzhou 350009,China;Department of Obstetrics,the First Affiliated Hospital of Fujian Medical University,Fuzhou 350009,China)

机构地区：[1]福建医科大学附属福州市第一医院检验科,福州350009 [2]福建医科大学附属福州市第一医院产科,福州350009

出　　处：《中华围产医学杂志》2023年第2期109-112,共4页Chinese Journal of Perinatal Medicine

基　　金：福州市科技计划项目(2021-S-173)。

摘　　要：目的探讨16p12.2拷贝数变异的产前超声和遗传学诊断。方法回顾性分析2017年1月至2021年12月在福建医科大学附属福州市第一医院行产前诊断的7例16p12.2微缺失/重复胎儿的产前诊断指征、产前超声表现、染色体核型、遗传学分析、变异溯源、妊娠结局及出生后随访情况等。对数据进行描述性统计分析。结果 3例为产前超声结构异常, 包括多发畸形、室间隔缺损及唇腭裂各1例;其余4例为涉及心脏和肾脏的软指标异常。7例胎儿染色体核型分析均未见异常。单核苷酸多态性微阵列(single nucleotide polymorphism array, SNP array)检测结果显示, 4例16p12.2(远端)微缺失病例缺失的片段大小为381.7~542.4 kb, 均包含OTOA、METTL9和IGSF6等3个在线人类孟德尔遗传数据库(Online Mendelian Inheritance in Man, OMIM)基因;另3例16p12.2(近端)微缺失/重复的片段大小为484.0~701.7 kb, 均包含UQCRC2、CDR2、EEF2K和POLR3E等4个OMIM基因。7例16p12.2微缺失/重复病例中, 5例(例1、2、4、5、6)变异遗传自表型正常的母亲/父亲, 其中3例(例2、4、5)足月分娩, 出生情况正常;2例(例3、7)拒绝行家系验证。例3足月分娩, 3个月行室间隔缺损修补术, 随访至18个月未见明显异常。结论 16p12.2区域微缺失/重复胎儿产前缺乏特异性表型。OTOA基因是16p12.2远端区域异常关键基因。家系比对有助于减少不必要的主动终止妊娠。Objective To investigate the prenatal ultrasonographic features and diagnosis of 16p12.2 copy number variation(CNV).Methods This retrospective study recruited seven fetuses with 16p12.2 microdeletion/microduplication in the First Affiliated Hospital of Fujian Medical University from January 2017 to December 2021.Data,including the prenatal diagnostic indications,ultrasound findings,karyotypes,genetic testing and mutation tracing results,pregnancy outcomes,and postnatal follow-up data,were summarized with descriptive statistical analysis.Results Prenatal ultrasound indicated three fetuses with structural abnormalities,including one case each of multiple malformations,interventricular septal defect,and cleft lip and palate.The other four cases were positive for ultrasonic soft markers involving the heart and kidney.The chromosome karyotypes of the seven fetuses were normal.Single nucleotide polymorphism array(SNP array)results showed that four cases had a 381.7-542.4 kb microdeletion containing three genes(OTOA,METTL9,and IGSF6)in Online Mendelian Inheritance in Man(OMIM)at 16p12.2(distal region)and three cases had a 484.0-701.7 kb microdeletion/microduplication containing four OMIM genes(UQCRC2,CDR2,EEF2K,and POLR3E)at 16p12.2(proximal region).Five(cases 1,2,4,5,and 6)out of the seven fetuses inherited the variants from their phenotypically normal mother/father,and among them,three(cases 2,4,and 5)were delivered at term and healthy.Two cases(cases 3 and 7)refused to undergo pedigree verification.Case 3,a full-term infant,underwent ventricular septal defect repair three months after birth,and no abnormality was found at 18 months of age.Conclusions No specific phenotype presents in fetuses with 16p12.2 microdeletion/microduplication in prenatal diagnosis.OTOA gene is the key gene associated with abnormality in the distal region of 16p12.2.Pedigree analysis is conducive to preventing unnecessary termination of pregnancy.

关 键 词：染色体缺失 染色体重复 染色体 人 16对 DNA拷贝数变异 多态性 单核苷酸 产前诊断 

分 类 号：R714.5[医药卫生—妇产科学]