MPZ基因新发移码突变致CMT患儿1例的临床表型及遗传学分析  

Clinical and genetic analysis of a child with CMT caused by a new frameshift mutation of MPZ gene

作　　者：朱岩 赵向宇 高春海[2,3] 车峰远 Zhu Yan;Zhao Xiangyu;Gao Chunhai;Che Fengyuan(Department of Neurology,11 Affiliated Clinical Medical of Qingdao University,Jining No.1 People’s Hospital,Jining 272000,China;Department of Laboratory Medicine,Linyi People’s Hospital,Linyi 276000,China;Key Laboratory for Laboratory Medicine of Linyi City,Linyi 276000,China;Department of Neurology,Linyi People’s Hospital,Linyi 276000,China)

机构地区：[1]青岛大学第十一临床医学院,济宁市第一人民医院神经内科,济宁272000 [2]临沂市人民医院检验医学中心,临沂276000 [3]临沂市检验医学重点实验室,临沂276000 [4]临沂市人民医院神经内科,临沂276000

出　　处：《国际遗传学杂志》2024年第6期454-460,共7页International Journal of Genetics

基　　金：山东省自然科学基金(ZR2020QH047)。

摘　　要：目的对一例腓骨肌萎缩症(charcot-marie-tooth disease,CMT)患儿进行临床表征及基因变异分析。方法2019年4月在济宁市第一人民医院就诊患儿1例,通过病史采集、体格检查、神经系统发育量表评估、影像学以及电生理检查进行表型分析。采集患儿及其家系成员外周血进行全外显子测序(whole exome sequencing,WES),对候选变异进行Sanger测序验证及生物信息学分析。结果临床电生理检测提示患儿有严重的脱髓鞘性神经病变伴继发性轴突变性,符合早发型CMT1B,并在正中神经和胫神经神经传导测定中记录到了传导阻滞和波形离散的电生理现象,提示了电生理表型的异质性,脑MRI提示左侧脑室管膜结节。WES结果显示患儿携带髓鞘蛋白零MPZ基因c.614dupC(p.Gly206Argfs*28)变异,该变异位于第5号外显子,未见相关数据库收录,为新发移码突变。该变异可导致截短蛋白的产生而影响MPZ蛋白的正常生理功能,ACMG判定为致病性突变。结论MPZ基因c.614dupC变异为本研究中CMT患儿的遗传学病因,该新发移码突变扩展了MPZ基因的致病突变谱。Objective To investigate the clinical characterization and gene variation in a child with charcot-marie-tooth disease(CMT).Methods In April 2019,a pediatric case was treated at Jining First People’s Hospital.Phenotypic analysis was performed by history collection,physical examination,neurological development scale assessment,imaging and electrophysiological examination.Peripheral blood of the proband and its family members were collected for whole exome sequencing(WES),Sanger sequencing validation and bioinformatics analysis of candidate variants.Results Clinical electrophysiological tests showed that the child had severe demyelinating neuropathy with secondary axonal degeneration,which was consistent with early-onset CMT1B and the electrophysiological phenomena of conduction block and waveform dispersion were recorded in the median nerve and tibial nerve conduction assays,suggesting the heterogeneity of electrophysiological phenotypes,and brain MRI showed left ventricular ependymal nodules.The WES results showed that the proband carried the myelin protein zero(MPZ)gene c.614dupC(p.Gly206Argfs*28)mutation,which was located in exon 5 and was not included in the relevant database,which was a new frameshift mutation.This variation can lead to the production of truncated protein and affect the normal physiological function of MPZ protein,and ACMG is judged to be a pathogenic mutation.Conclusion The c.614dupC variant of MPZ gene is the genetic cause of children with CMT in this study,and this new frameshift mutation also expands the pathogenic mutation spectrum of MPZ gene.

关 键 词：腓骨肌萎缩症 移码突变 基因型 表型 髓鞘蛋白零 

分 类 号：R73[医药卫生—肿瘤]