非免疫性胎儿水肿综合征的遗传学因素及妊娠结局分析  

Genetic etiology and pregnancy outcome of non-immune fetal edema syndrome:a Chinese cohort study

作　　者：丁丽娜 高智霖 张慧敏[1] 何文智[1] 李少英[1] 陈敏[1] 陈菲[1] 翦薇[1] 李南[1] 谢亦农[1] 李志华[1] Ding Lina;Gao Zhilin;Zhang Huimin;He Wenzhi;Li Shaoying;Chen Min;Chen Fei;Jian Wei;Li Nan;Xie Yinong;Li Zhihua(Obstetric of Gynecology and Gynecology,The Third Affiliated Hospital of Guangzhou Medical University,Guangzhou Medical Center for Critical Pregnant Women,Guangdong Province Key Laboratory of Major Obstetric Diseases,Key Laboratory for Reproduction and Genetics of Guangdong Higher Education Institutes,Guangzhou 510150,China;Deportment of Obstetrics,Central Hospital of Dongguan,Affiliated Dongguan Shilong People′s Hospital of Southorn Medical University,Dongguan 523000,China)

机构地区：[1]广州医科大学附属第三医院妇产科,广州重症孕产妇救治中心,广东省产科重大疾病重点实验室,广东省普通高校生殖与遗传重点实验室510150 [2]广东省,东莞市松山湖中心医院产科,南方医科大学附属东莞石龙人民医院,523000

出　　处：《中华产科急救电子杂志》2022年第1期38-45,共8页Chinese Journal of Obstetric Emergency（Electronic Edition）

基　　金：广东省自然科学基金(2018A0303130298)。

摘　　要：目的探讨非免疫性胎儿水肿综合征(nonimmune hydrops fetalis,NIHF)非重型α地中海贫血胎儿的遗传学原因及妊娠结局。方法回顾性分析2014年1月至2020年7月在广州医科大学附属第三医院超声诊断为非免疫性胎儿水肿综合征病例116例,通过染色体核型分析/染色体微阵列分析(chromosome microarray analysis,CMA)/全外显子组测序(whole exome sequencing,WES)进行产前诊断,并分析其妊娠结局。结果103例单胎NIHF中45例(43.69%,45/103)有临床显著的产前诊断结果异常,其中30例染色体数目异常,9例有致病性/可能致病性拷贝数变异,6例有致病性/可疑致病/临床意义未明的变异。13例双胎及多胎之一NIHF中5例为非整倍体。81例单胎选择人工终止妊娠。19例单胎继续妊娠,除8例胎死宫内外,11例活产(6例早产,5例足月产);其中4例(3例早产、1例足月产)接受了出生后手术(1例行室间隔修补术,1例行腹腔穿刺引流术,1例行回肠双腔造口术,1例行肠梗阻手术),3例成功,1例术后夭折;6例未行手术者除1例生长发育迟缓,余生长发育正常。结论NIHF主要的遗传学病因是非整倍体异常、CNV异常及点突变,CMA对胎儿遗传学病因的检出率高于染色体核型分析,应被用于一线检查手段;WES是诊断NIHF的一个非常有价值的工具,可以发现罕见单基因遗传病。Objective To investigate the genetic causes and pregnancy outcome of nonimmune hydrops fetalis(NIHF).Methods We retrospectively recruited 116 cases of hydrops fetalis diagnosed by ultrasound in our hospital from January 2014 to July 2020.All the cases were undergone prenatal diagnosis by at least one of the following tests:(1)karyotyping,(2)chromosomal microarray analysis(CMA)or (3)whole exome sequencing(WES).The medical records of pregnancy outcome was retrieved and analyzed.Results Among 103 singleton pregnancies with NIHF,45 cases(43.69%,45/103)were reported to have clinically significant results including 30 cases with numerical disorders,9 cases with pathogenic or likely pathogenic copy number variants(CNVs)and 6 cases with point mutations.Among 13 twin and multiple pregnancies with NIHF,5 cases were diagnosed as aneuploidies.For the pregnancy outcome,81singleton pregnancies were ended with termination of pregnancy.19 singleton pregnancies chose to continue the pregnancy,except 8 cases died in utero.The remaining 11 cases were all live births,among which 6 cases were born premature and 5 cases were full-term.4 cases(3 cases were premature,1 case was in term deliveries)received post-birth surgical intervention,of which 3 cases were successful and 1 case died after operation.Among 6 cases without surgical intervention,1 case had growth retardation and the other 5 cases manifested normal growth and development.Conclusions Numerical disorders,CNV disorders and point mutations are the main genetic causes of NIHF.The detection rate of CMA in NIHF is higher than chromosome karyotype analysis,so CMA should be used as a first-line method for genetic investigation of NIHF.WES is a valuable tool for the diagnosis of NIHF due to the ability to detect rare single-gene disorders.

关 键 词：胎儿水肿 核型分析 微阵列分析 外显子测序 妊娠结局 

分 类 号：R714.5[医药卫生—妇产科学]