一例全前脑畸形胎儿的临床及遗传学分析  

Clinical features and genetic analysis of a fetus with holoprosencephaly

作　　者：虞金哲 李闯 张琰[2] 李岭 吕远[1] 崔红[1] Yu Jinzhe;Li Chuang;Zhang Yan;Jesse Li-Ling;Lyu Yuan;Cui Hong(Department of Gynecology and Obstetrics,Shengjing Hospital Affiliated to China Medical University,Key Laboratory of Maternal-Fetal Medicine of Liaoning Province,Shenyang,Liaoning 110004,China;Obstetric Outpatient Clinic,Shenyang Woman's and Children's Hospital,Shenyang,Liaoning 110011,China;State Key Laboratory of Biotherapy,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,China)

机构地区：[1]中国医科大学附属盛京医院妇产科、辽宁省母胎医学重点实验室,沈阳110004 [2]沈阳市妇婴医院产科门诊,110011 [3]四川大学华西医院生物治疗国家重点实验室,成都610041

出　　处：《中华医学遗传学杂志》2020年第5期547-550,共4页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(81701462);辽宁省产科疾病临床医学研究中心及协同网络建设(2016007014)。

摘　　要：目的明确一全前脑畸形胎儿的致病原因,为该家系的遗传咨询提供依据。方法收集胎儿的孕期超声资料,应用全外显子测序技术(whole exon sequencing,WES)检测患儿的致病原因,低深度高通量测序技术对胎儿及其父母进行染色体拷贝数变异(copy number variant,CNV)检测,染色体细胞培养方法分析夫妻双方核型。结果胎儿孕期超声提示胎儿脑部结构异常,经诊断后明确为全前脑畸形。WES结果提示胎儿13号染色体存在约33 Mb片段缺失,缺失区域包含1个单倍剂量敏感基因ZIC2。染色体CNV检测结果提示胎儿13号染色体13q31.1-34区域存在32.32 Mb缺失,而夫妻双方均未发现相同的染色体片段缺失。夫妻双方核型分析结果未发现染色体大的结构改变。结论根据临床资料胎儿确诊为全前脑畸形,遗传学检测明确其致病原因为包含单倍剂量敏感基因ZIC2的13号染色体片段缺失。Objective To analyze the clinical features and pathogenesis of a fetus with holoprosencephaly.Methods The findings of prenatal ultrasonography was reviewed.Following elective abortion,whole exome sequencing(WES)was carried out to identify potential pathogenic variant.Copy number variants(CNVs)of the abortus and its parents were detected by low-depth high-throughput sequencing.The parents were also analyzed by chromosomal karyotyping.Results Prenatal ultrasound suggested that the fetus had holoprosencephaly.WES revealed that it had approximately 33 Mb deletion at chromosome 13 involving ZIC2,a haploid dose sensitive gene.The results of low-depth high-throughput sequencing confirmed that the fetus carried a de novo 32.32 Mb deletion at 13q31.1-34.Karyotyping analysis has excluded gross chromosomal aberration in both parents.Conclusion The fetus was diagnosed with holoprosencephaly,which may be attributable to the 13q31.1-34 deletion involving the ZIC2 gene.

关 键 词：全前脑畸形 全外显子测序 染色体拷贝数变异 ZIC2基因 

分 类 号：R714[医药卫生—妇产科学]