PRF1突变致家族性嗜血细胞综合征二例  

two cases of familial hemophilic lymphohistiocytosis in children caused by PRF1 mutation

作　　者：王丽辉[1] 杜雅坤[1] 刘兰 陈芳[1] WangLihui;Du Yakun;Liu Lan;Chen Fang(Department of Neurology,the Hebei Children's Hospital,Shijiazhuang 050031,China)

机构地区：[1]河北省儿童医院神经内科,石家庄050031

出　　处：《脑与神经疾病杂志》2024年第4期221-225,共5页Journal of Brain and Nervous Diseases

基　　金：河北省医学科学研究课题计划项目(20240744)。

摘　　要：目的探讨PRF1基因突变致家族性嗜血细胞淋巴组织细胞增多症2型(FLH2型)临床症状和基因型特点。方法报道2例河北省儿童医院神经内科住院一家系患儿的临床资料,提取患儿及其父母基因组DNA,采取靶向外显子捕获测序技术检测致病突变,并对检测到的突变进行Sanger测序验证。结果该家系2例患儿均以共济失调为首发症状,病情反复,查脑脊液白细胞数升高,头颅MRI提示多发脱髓鞘改变。基因检测显示为PRF1基因突变c.1189-1190dupTG(p.H398Afs*23)和c.394G>A(p.G132R)的复合杂合子,前者来自于父亲,后者来自于母亲。妹妹给予干细胞移植治疗,目前病情缓解。结论PRF1基因突变致FLH2型符合基因杂合变异遗传学特点。儿童可以中枢神经系统受累为首发症状,表现为共济失调、周围性面神经瘫痪,基因可早期诊断,干细胞移植治疗是获得长期生存的方法之一。Objective To investigate the clinical features of familial hemophilic lymphohistiocytosis type 2(FLH2)in children caused by PRF1 mutation.Methods The clinical data of 2 children hospitalized in the Department of Neurology of Hebei Children's Hospital were reported,and the genomic DNA of the children and their parents was extracted.Targeted exon capture sequencing technology was used to detect the pathogenic mutation,and the detected mutation was verified by Sanger sequencing.Results Both children in this family had ataxia as the first symptom.relapse of illness.The number of leukocytes in the cerebrospinal fluid was increased,and brain MRI showed multiple demyelinating changes.the children was compound heterozygotes of PRF1 mutation c.1189-1190dupTG(p.H398Afs*23)and c.394G>A(p.G132R),the former from the father and the latter from the mother.The younger sister in stable condition was given stem cell transplantation treatment.Conclusion FLH2 caused by PRF1 mutation is consistent with the genetic characteristics of gene hybridization and variation.In children,central nervous system involvement may be the first symptom.Manifested as ataxia,peripheral facial palsy,gene could be diagnosed early,and Stem cell transplantation is one of the ways to achieve long-term survival.

关 键 词：家族性嗜血细胞淋巴组织细胞增多症2型 PRF1基因 儿童 共济失调 中枢神经系统炎症 干细胞移植 

分 类 号：R741[医药卫生—神经病学与精神病学]