Wolf-Hirschhorn综合征相关胎儿宫内生长受限表型关键区域的鉴定  

Identification of a critical region on chromosome 4p16.3 for Wolf-Hirschhorn syndrome-associated fetal growth retardation

作　　者：郑文婷 陈宝江[2] 尹志军 黄雪珍 梁映亮 Zheng Wenting;Chen Baojiang;Yin Zhijun;Huang Xuezhen;Liang Yingliang(Department of Laboratory Medicine,Xiaolan Hospital of Southern Medical University,Zhongshan,Guangdong 528415,China;Fetal Medicine Center,Department of Obstetics and Gynecology,First Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong 510080,China)

机构地区：[1]南方医科大学附属小榄医院检验科,中山528415 [2]中山大学附属第一医院产科胎儿医学中心,广州510080

出　　处：《中华医学遗传学杂志》2020年第7期731-735,共5页Chinese Journal of Medical Genetics

摘　　要：目的探讨Wolf-Hirschhorn综合征(Wolf-Hirschhorn syndrome,WHS)胎儿的产前超声表型特征,并分析胎儿生长受限(fetal growth retardation,FGR)表型的关键区域。方法回顾2262例产前超声异常胎儿的染色体核型和染色体微阵列分析结果,总结WHS胎儿的产前超声表型特征及其4p缺失片段的差异,并结合文献报道的孤立性4p缺失的WHS病例,分析4p缺失片段的最小重叠区域(smallest region of overlap,SRO),以确定FGR表型的关键区域。结果在2262例超声异常胎儿中,共检出10例4p缺失的WHS。这10例胎儿均表现出FGR。结合文献报道的80例患者进行统计分析,结果显示WHS最常见的产前超声表型为FGR,占76.7%。对于FGR相关SRO的定位分析提示,4p16.3区1.32~1.74 Mb的位置存在一个SRO,其大小约419 kb,包含7个蛋白质编码基因:TACC3、SLBP、TMEM129、FAM53A、MAEA、UVSSA及CRIPAK。结论WHS胎儿最常见的产前超声表型为FGR。4p16.3区1.32~1.74 Mb的位置可能是FGR表型的关键区域,所包含的TACC3和SLBP可能是FGR的候选基因。Objective To analyze ultrasonographic finding in fetuses with Wolf-Hirschhorn syndrome(WHS)and refine the critical region on chromosome 4p16.3 for WHS-associated fetal growth retardation(FGR).Methods In total 2262 fetuses with abnormal ultrasonographic findings who underwent prenatal karyotyping and chromosomal microarray analysis were reviewed.WHS-associated 4p deletions detected in these fetuses were compared,and prenatal ultrasound findings in such fetuses were summarized.Meanwhile,WHS cases with prenatal ultrasound findings and isolated 4p deletions in previous studies were included for further analysis.An analysis of smallest region of overlap(SRO)among discrepant 4p deletions in these cases above was performed to define a critical region for FGR.Results 4p deletions were detected in 10 of the 2262 fetuses and 5.0%of the 202 fetuses with FGR.Combined with 80 WHS cases from previous studies,the most common prenatal ultrasound finding was FGR,which yielded a frequency of 76.7%.In addition,a SRO spanning approximately 419 kb(genomic position:1.32-1.74 Mb)on chromosome 4p16.3 was discovered by comparing the unusual 4p deletions among the 10 fetuses.The region contained seven protein-coding genes,including TACC3,SLBP,TMEM129,FAM53A,MAEA,UVSSA and CRIPAK.Conclusion For fetuses with WHS,the most common prenatal ultrasound phenotype was FGR.A region between 1.32 Mb to 1.74 Mb from the telomere on chromosome 4p16.3 is critical for WHS-associated FGR,for which TACC3 and SLBP are the candidate genes.

关 键 词：Wolf-Hirschhorn综合征 4p缺失 胎儿生长受限 染色体微阵列分析 

分 类 号：R714.5[医药卫生—妇产科学]