ZEB2基因所致Mowat-Wilson综合征2例患儿的遗传学分析  

Clinical features and genetic analysis of two children with Mowat-Wilson syndrome due to variants of ZEB2 gene

作　　者：韩春晓 闫露露 张玉鑫 李海波 Han Chunxiao;Yan Lulu;Zhang Yuxin;Li Haibo(The Central Laboratory of Birth Defects Prevention and Control,the Affiliated Women and Children′s Hospital of Ningbo University,Ningbo,Zhejiang 315012 China;Ningbo Key Laboratory for the Prevention and Treatment of Embryogenic Diseases,the Affiliated Women and Children′s Hospital of Ningbo University,Ningbo,Zhejiang 315012 China;Ningbo Key Laboratory of Genomic Medicine and Birth Defects Prevention,the Affiliated Women and Children′s Hospital of Ningbo University,Ningbo,Zhejiang 315012 China)

机构地区：[1]宁波大学附属妇女儿童医院出生缺陷综合防治中心 [2]宁波市胚胎源性疾病防治重点实验室 [3]宁波市基因组医学与出生缺陷防治重点实验室

出　　处：《中华医学遗传学杂志》2024年第12期1448-1455,共8页Chinese Journal of Medical Genetics

基　　金：宁波市重点研发计划(2023Z178);宁波市医疗卫生高端团队项目(2022020405);宁波市社会公益项目(2022S035);"宁波市科创甬江"2035计划项目(2024Z221)。

摘　　要：目的探讨2例Mowat-Wilson综合征(MWS)患儿的遗传学病因。方法选取分别于2022年5月1日和2022年10月17日就诊于宁波大学附属妇女儿童医院的2例患儿作为研究对象,收集其相关的临床资料,对患儿进行全外显子组测序(WES),对候选变异进行Sanger测序家系验证及致病性分析。本研究通过了宁波大学附属妇女儿童医院医学伦理委员会的审查(批准号:EC2020-014)。结果患儿1为3岁男性,表现为癫痫。颅脑MRI提示胼胝体发育不良,双眼内斜、肌张力低、发育迟缓、反复便秘。WES检测显示患儿1携带ZEB2基因c.262dupT(p.Ile88Asnfs*31)杂合移码变异,其父母均为野生型。患儿2为6月龄男性,表现为癫痫、发育迟缓、倒睫、房间隔缺损、隐睾。颅脑MRI检查未见明显异常。WES检测显示其携带ZEB2基因c.3213_3224delinsCTAC(p.Q1072Yfs*49)移码变异,其父母均为野生型。根据美国医学遗传学与基因组学学会相关指南,上述变异均被判定为可能致病性(PVS1+PM2_Supporting+PM6;PVS1_Strong+PM2_Supporting+PM6),导致终止密码子提前出现。结论结合2例患儿的临床表型及基因检测结果,确诊其为ZEB2基因变异导致的MWS。上述发现丰富了MWS患者ZEB2基因的变异谱。ObjectiveTo explore the clinical features and genetic variants in two children with Mowat-Wilson syndrome(MWS).MethodsTwo children admitted to the Affiliated Women and Children′s Hospital of Ningbo University On May 1,2022 and Oct 17,2022 were selected as the study subjects.Clinical data of the patients were collected.The two children were subjected to whole exome sequencing.Candidate variants were verified by Sanger sequencing and bioinformatic analysis.This study has been approved by the Medical Ethics Committee of the Women and Children′s Hospital of Ningbo University(Ethic No.EC2020-014).ResultsChild 1 was a 3-year-old male who had presented with epilepsy.Cranial MRI revealed hypoplasia of corpus callosum,down-slanting eyes,hypotonia,developmental delay,and recurrent constipation.The child was found to harbor a de novo c.262dup(p.Ile88Asnfs*31)missense variant of the ZEB2 gene,which was detected in neither parents.Child 2 was a 6-months-old male presented with epilepsy,with no apparent anomaly detected by cranial MRI.The child had featured developmental delay,inverted eyelash,atrial septal defect,and cryptorchidism.WES revealed that he had harbored a c.3213_3224delinsCTAC(p.Q1072Yfs*49)frameshifting variant of the ZEB2 gene,which was detected in neither parents.Based on the guidelines from the American College of Medical Genetics and Genomics,both variants were determined as likely pathogenic,with ratings of PVS1_Strong+PM2_Supporting+PM6 and PVS1_Strong+PM2_Supporting+PM6.Both variants had resulted in premature occurrence of stop codons.ConclusionBy combining their clinical features and results of genetic testing,both children had been diagnosed with MWS due to variants of the ZEB2 gene.Above findings have enriched the mutational spectrum of MWS and provided a basis for the prenatal diagnosis and genetic counseling.

关 键 词：Mowat-Wilson综合征 ZEB2基因 全外显子组测序 

分 类 号：R725.9[医药卫生—儿科]