一例嵌合型Beckwith-Wiedemann综合征的分子诊断与分析  

Molecular Diagnosis and Analysis of A Fetus with Chimeric Beckwith-Wiedemann Syndrome

作　　者：郭静 朱重阳 李鹏云[1] 王涵铎 刘灵[1] GUO Jing;ZHU Chongyang;LI Peng-yun;WANG Han-duo;LIU Ling(Prenatal Diagnostic Center,The Third Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第三附属医院产前诊断中心,450052

出　　处：《国际妇产科学杂志》2023年第4期442-445,共4页Journal of International Obstetrics and Gynecology

基　　金：河南省重点研发与推广专项(科技攻关)(212102310471)。

摘　　要：报告1例产前超声提示左肾囊肿、羊水偏多的孕妇行产前诊断,经咨询后要求对胎儿进行遗传学检测,以明确临床诊断。采用染色体微阵列分析(chromosomal microarray analysis,CMA)和全外显子组测序(whole exome sequencing,WES)技术对胎儿羊水细胞DNA进行分析。CMA检测结果显示胎儿染色体11p15.5p15.1区域存在片段大小约为18.6 Mb的嵌合型单亲二体(uniparental disomy,UPD);WES检测范围内未发现明确的致病性基因变异。为明确胎儿嵌合型UPD的亲本来源,进一步采用甲基化特异性多重连接探针扩增技术(methylation-specific multiplex ligationdependent probe amplification,MS-MLPA)检测胎儿印迹区域甲基化异常情况,结果显示胎儿印迹中心域1(imprinting center region 1,ICR1)区甲基化水平升高,ICR2区甲基化水平降低,因此可判定胎儿11p15.5p15.1区域为父源性嵌合UPD,从而确诊胎儿为Beckwith-Wiedemann综合征(Beckwith-Wiedemann Syndrome,BWS)。BWS产前超声常为非特异性表现,极易造成漏诊和误诊,因此选择正确且有针对性的分子诊断技术异常重要,避免缺陷患儿的出生。A pregnant woman with left renal cyst and excessive amniotic fluid diagnosed by prenatal ultrasound was reported.After consultation,genetic testing of the fetus was requested to clarify the clinical diagnosis.Subsequently,chromosomal microarray analysis(CMA)and whole exome sequencing(WES)were used to analyze the DNA of fetal amniotic fluid cells.CMA results showed that there was a chimeric uniparental disomy(UPD)with a fragment size of about 18.6 Mb in the 11p15.5p15.1 region of the fetal chromosome.Simultaneously,no clear pathogenic gene mutations were found within the WES detection range.To clarify the parental origin of fetal chimeric UPD,the methylation-specific multiplex ligation-dependent probe amplification(MS-MLPA)for Beckwith-Wiedemann syndrome(BWS)was further used to detect abnormal methylation in the fetal imprinted region.The MS-MLPA results demonstrated that the methylation level in the imprinting center region 1(ICR1)region of the fetus increased,while the methylation level in the ICR2 region decreased.Therefore,it can be determined that the fetal 11p15.5p15.1 region is a paternal chimeric UPD,thereby confirming that the fetus is BWS.Prenatal ultrasound of BWS is often a non-specific manifestation,which easily leads to missed diagnosis and misdiagnosis.Therefore,it is extremely important to carry out correct and targeted molecular diagnostic techniques to avoid the birth of defective children.

关 键 词：BECKWITH-WIEDEMANN综合征 单亲二体性 染色体 微阵列分析 甲基化 产前诊断 

分 类 号：R714.55[医药卫生—妇产科学]