脑组织铁沉积神经变性病患儿临床及遗传学分析六例  

Clinical and genetic analysis of six children with neurodegeneration with brain iron accumulation

作　　者：张美[1] 谭自明 王君[1] 谢佳琳[1] 罗琼[1] Zhang Mei;Tan Ziming;Wang Jun;Xie jialin;Luo Qiong(Department of Pediatric Neurology,First Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China)

机构地区：[1]新疆医科大学第一附属医院小儿神经内科,乌鲁木齐830011

出　　处：《中华临床医师杂志(电子版)》2024年第10期931-942,共12页Chinese Journal of Clinicians(Electronic Edition)

基　　金：乌鲁木齐自治区自然科学基因(2021D01C313)

摘　　要：目的对6名患有脑组织铁沉积神经性变性病的儿童进行临床及遗传方面的研究。方法对2021年3月~2024年6月在新疆医科大学第一附属医院就诊的6例脑组织铁沉积神经变性病患儿的临床表现及影像学资料进行回顾性分析,并利用全外显子检测技术对患儿及家属进行基因测序。结果6例患儿中包括4例女孩和2例男孩,就诊年龄为1岁7个月至6岁,临床均表现出全面性发育迟缓,2例患儿呈现明显倒退性病程,其中1例患儿患有重症肌无力(眼肌型)。基因测序显示,4例患儿存在WDR45基因突变,分别为c.519+1_519+3del、c.381del、c.984C>G、c.400C>T,经桑格测序验证均为新生突变;2例存在PLA2G6基因突变,其中1例同时携带c.1547_1548dupCG(重复变异)及c.1799G>A2个基因突变位点,另1例突变位点为c.1002dupA。结论脑组织铁沉积神经变性病具有临床及遗传多样性,全外显子基因测序、结合病史及MRI可助于早期诊断并指导治疗,新变异位点的检出拓宽了基因变异谱。Objective To investigate the clinical and genetic feasures of children with neurodegeneration with brain iron accumulation.Methods A retrospective analysis was conducted on the clinical manifestations and imaging data of six children with neurodegeneration with brain iron accumulation who were treated at the First Affiliated Hospital of Xinjiang Medical University from March 2021 to June 2024.Gene sequencing was performed on the children and their families using whole exome technology.Results Among the six pediatric patients,four were girls and two were boys,with ages ranging from 1 year and 7 months to 6 years old.All patients presented with comprehensive developmental delay clinically,and two patients showed significant developmental regression.Among them,one patient had myasthenia gravis(ocular muscle type).Gene sequencing showed that four children had WDR45 gene mutations,namely,c.519+1_519+3del c.381del,c.984C>G,and c.400C>T.After Sanger sequencing verification,all mutations were found to be de novo.Two cases had PLA2G6 gene mutations,with one case carrying both c.1547_1548dupCG(repeat mutation)and c.1799G>A gene mutations,and the other case carrying c.1002dupA mutation.Conclusion Neurodegeneration with brain iron accumulation has clinical and genetic diversity.Whole exome gene sequencing,combined with medical history and MRI,can help with early diagnosis and guide treatment.The detection of new mutation sites broadens the spectrum of gene variation.

关 键 词：脑组织铁沉积神经变性病 WDR45基因 PLA2G6基因 基因突变 全外显子测序 X连锁显性遗传 

分 类 号：R741[医药卫生—神经病学与精神病学]