NEB基因变异所致杆状体肌病1例患儿的遗传学分析  

Genetic analysis of a patient with Rod-shaped myopathy due to variants of NEB gene

作　　者：郑伟荣 彭小燕 雷宇清 王力文 王心睿 赵倩倩 Zheng Weirong;Peng Xiaoyan;Lei Yuqing;Wang Liwen;Wang Xinrui;Zhao Qianqian(The Central Laboratory of Birth Defects Prevention and Control,The Affiliated Women and Children′s Hospital of Ningbo University,Ningbo,China;Ningbo Key Laboratory for the Prevention and Treatment of Embryogenic Diseases,The Affiliated Women and Children′s Hospital of Ningbo University,Ningbo,China;Ningbo Key Laboratory of Genomic Medicine and Birth Defects Prevention,The Affiliated Women and Children′s Hospital of Ningbo University,Ningbo,China;不详)

机构地区：[1]福建省儿童医院(上海儿童医学中心福建医院),福州350011 [2]福建省妇幼保健院医学研究中心,福州350005 [3]国家卫生健康委员会非人灵长类生育调节技术评价重点实验室(福建省妇幼保健院),福州350005 [4]福建省妇产医院(福建省妇幼保健院五四北分院),福州350013

出　　处：《中华医学遗传学杂志》2024年第12期1473-1477,共5页Chinese Journal of Medical Genetics

摘　　要：目的探讨1例杆状体肌病患儿的遗传学病因。方法选取2023年1月28日因"喉中痰鸣1月余"就诊于福建省儿童医院的1例患儿作为研究对象。收集患儿的临床资料。采集患儿及其父母的外周血样,提取DNA,进行全外显子组测序(WES),并对候选变异进行Sanger测序家系验证和致病性分析。本研究通过了福建省儿童医院医学伦理委员会的审查(批准号:2023ETKLRK2004)。结果患儿为2月龄女性,表现为持续喉中痰鸣、反复重症肺炎、吞咽异常和肌张力减退等。WES检测结果提示患儿携带NEB(NM_001271208.1)基因c.4611+2T>A/c.12961del(p.Ser4321ALafs*21)复合杂合变异,相关疾病为杆状体肌病,Sanger测序证实上述变异分别遗传自其表型正常的母亲和父亲。根据美国医学遗传学与基因组学学会(ACMG)相关指南,上述变异均被评级为可能致病性(PVS1_Moderate+PM2_Supporting+PM3;PVS1+PM2_Supporting)。结论NEB基因c.4611+2T>A/c.12961del(p.Ser4321ALafs*21)复合杂合变异可能是该患儿的遗传学病因。上述发现对患儿的诊断、遗传咨询及其父母的再生育指导提供了依据。ObjectiveTo explore the genetic etiology of a child with Nemaline myopathy(NM).MethodsA child who had visited Fujian Children′s Hospital on January 28,2023 due to"phlegm in the throat for more than a month"was selected as the study subject.Clinical data of the child was collected,in addition with peripheral blood samples from her and her parents.Following extraction of genomic DNA,trio-whole exome sequencing(WES)was carried out.Candidate variants was verified by Sanger sequencing and bioinformatic analysis.This study has been approved by the Medical Ethics Committee of Fujian Children′s Hospital(Ethic No.2023ETKLRK2004).ResultsThe patient,a 2-month-old female,had presented with persistent phlegm in the throat,recurrent severe pneumonia,swallowing difficulty,and decreased muscle tone.WES results revealed that she has harbored compound heterozygous variants of the NEB(NM_001271208.1)gene,namely c.4611+2T>A and c.12961del(p.Ser4321ALafs*21),and the associated disease is rod-like myopathy.Sanger sequencing confirms that the variants were respectively inherited from her mother and father,both of whom had normal phenotypes.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),both variants were rated as likely pathogenic(PVS1_Moderate+PM2_Supporting+PM3;PVS1+PM2_Supporting).ConclusionThe c.4611+2T>A/c.12961del(p.Ser4321ALafs*21)compound heterozygous variants of the NEB gene probably underlay the pathogenesis in this child.Above findings has facilitated the diagnosis,genetic counseling,and guidance for reproductive decision of her family.

关 键 词：杆状体肌病 NEB基因 基因变异 全外显子组测序 

分 类 号：R725.9[医药卫生—儿科]