急性坏死性脑病合并脊髓性肌萎缩症1例  

A case of acute necrotizing encephalopathy combined with spinal muscular atrophy

作　　者：彭红艳 梁宇峰 武志远 梁卓信 胡培丹 Peng Hongyan;Liang Yufeng;Wu Zhiyuan;Liang Zhuoxin;Hu Peidan(Department of Pediatric Intensive Care Unit,Guangzhou Women and Children’s Medical Center,Guangzhou Medical University,Guangzhou 510120,China;Department of Intensive Care Medicine,Liuzhou Hospital,Guangzhou Women and Children’s Medical Center,Liuzhou 545005,China)

机构地区：[1]广州医科大学附属妇女儿童医疗中心PICU,广州510120 [2]广州市妇女儿童医疗中心柳州医院重症医学科,柳州545005

出　　处：《国际遗传学杂志》2024年第5期381-388,共8页International Journal of Genetics

基　　金：广州市卫生健康科技项目(20231A011031);广东省自然基金(2022A1515010556);西藏自治区自然科学基金组团式援藏医学项目[XZ2022ZR-ZY44(Z)]。

摘　　要：目的探讨1例急性坏死性脑病(acute necrotizing encephalopathy,ANE)合并脊髓性肌萎缩症(spinal muscular atrophy,SMA)患儿的临床特点及遗传学信息。方法收集广州医科大学附属妇女儿童医疗中心PICU诊治的1例ANE合并SMA患儿的临床资料,采用全外显子组测序、Sanger测序、多重连接探针扩增分析等基因检测技术对其家族人员进行遗传学分析。结果患儿,女,2.5岁,以发热、抽搐起病。脑脊液蛋白0.539 g/L、余脑脊液检查正常,头颅磁共振提示双侧丘脑异常信号。经过静脉免疫球蛋白、甲泼尼龙、降颅压等治疗,颅内病变减轻,精神运动能力均恢复。遗传学检测结果显示,患儿携带RANBP2基因的杂合错义突变(c.1754C>T,p.Thr585Met),根据美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)的指南初步判定为临床意义未明。同时,患儿还存在SMN1基因第7号外显子的纯合缺失,根据ACMG的指南初步判定为致病性变异(PVS1+PM3_Strong)。家系验证分析显示,父亲携带RANBP2基因的杂合变异,母亲及姐姐未见该变异;对于SMN1基因,父亲为杂合缺失,而母亲无缺失,姐姐为纯合缺失。结论RANBP2基因杂合错义突变(c.1754C>T,p.Thr585Met)可能是患儿易患ANE的遗传学病因。同时,患儿SMN1基因第7号外显子的纯合缺失表明其合并有SMA,为家族成员的遗传学咨询提供了有益线索。Objective This study aims to investigate the clinical features and genetic characteristics of a pediatric patient presenting with acute necrotizing encephalopathy(ANE)concurrent with spinal muscular atrophy(SMA).Methods Clinical data from a pediatric patient diagnosed with ANE and SMA and treated at the PICU of Guangzhou Medical University Women’s and Children’s Medical Center were collected.Genetic testing,including whole exome sequencing,Sanger sequencing,and multiplexed ligand probe amplification analysis,were performed on the patient and family members.Results The patient,a 2.5-year-old female,initially presented with fever and seizures.Cerebrospinal fluid protein levels were elevated at 0.539 g/L,with otherwise normal cerebrospinal fluid examination,while cranial magnetic resonance imaging revealed abnormal signals in the bilateral thalamus.Treatment with intravenous immunoglobulin,methylprednisolone,and cranial pressure reduction led to resolution of intracranial lesions and restoration of psychomotor abilities.Genetic testing revealed a heterozygous missense mutation(c.1754C>T,p.Thr585Met)in the RANBP2 gene,preliminarily classified as of undetermined clinical significance according to ACMG guidelines.Additionally,a homozygous deletion of exon 7 of the SMN1 gene was detected,initially deemed pathogenic according to ACMG guidelines(PVS1+PM3_Strong).Family validation analysis confirmed paternal inheritance of both variants.The sister also had homozygous deletion of exon 7 of SMN1 gene.Conclusion The heterozygous missense mutation in the RANBP2 gene may contribute to the patient’s susceptibility to ANE,while the homozygous deletion of exon 7 of the SMN1 gene indicates concurrent SMA,which provides valuable insights for genetic counseling of family members.

关 键 词：急性坏死性脑病 脊髓性肌萎缩症 RANBP2基因 SMN基因 

分 类 号：R746.4[医药卫生—神经病学与精神病学] R742[医药卫生—临床医学]