遗传性痉挛性截瘫7型临床特征及基因突变特点  

The clinical and genetic mutation features of hereditary spastic paraplegia 7

作　　者：张麟伟[1] 矫毓娟[1] 李小璇[1] 汪伟[1] 张伟赫[1] 彭丹涛[1] ZHANG Lin-wei;JIAO Yu-juan;LI Xiao-xuan(Department of Neurology,China-Japan Friendship Hospital,Beijing 100029,China)

机构地区：[1]中日友好医院神经科

出　　处：《中日友好医院学报》2019年第6期331-334,F0002,共5页Journal of China-Japan Friendship Hospital

基　　金：中日友好医院院级课题2018-2-QN-34

摘　　要：目的:分析并总结遗传性痉挛性截瘫7型(HSP7)患者的临床表现及基因突变特点。方法:收集2例HSP7患者的临床资料,完善头核磁平扫检查,行共济失调量表及认知功能量表评分,提取患者及其直系亲属外周血DNA,全外显子测序进行基因检测,结合一代测序验证突变位点。结果:2例HSP7患者临床表现均有走路不稳,小脑性共济失调、下肢肌张力增高、肌力减退及轻度认知功能减退,头核磁平扫发现轻度小脑萎缩,基因检测发现2例患者痉挛性截瘫7基因(SPG7)存在复合杂合突变,病例1:c.1047dupC(p.Gly349fs),c.1904C>T(p.Ser635Leu);病例2:c.2771delG(p.Met757fs),c.1529C>T(p.Ala510Val),均为已报道致病突变,家系验证证实突变分别来自于患者的父母且存在基因型-表型共分离。结论:HSP7患者临床上可以表现有小脑性共济失调及认知功能减退,本研究的2例HSP7患者经基因检测证实为SPG7基因复合杂合突变所致。Objective:To analyze and summarize the clinical features and gene mutations of hereditary spastic paraplegia 7(HSP7)patients.Methods:We summarized clinical manifestations and brain MRI features of two HSP7 patients,assessed the scale for the assessment and rating of ataxia(SARA)and mini-mental state exami-nation(MMSE)of the patients,and we extracted genomic DNA from the patients'peripheral blood and per-formed whole exome sequencing(WES)in two probands and verified in their unaffected parents and siblings.Results:In addition to walk unsteady and slightly spastic weakness of the lower extremities,both of the probands exhibited cerebellar dysfunction and mild cognitive decline.Their brain MRIs showed mild cerebellar atrophy.WES identified compound heterozygous mutations in SPG7 gene in both patients were c.1047dupC(p.Gly349fs),c.1904C>T(p.Ser635Leu);and c.1529C>T(p.Ala510Val),c.2771delG(p.Met757fs).The four mutations were reported before.Sanger sequencing was performed and revealed the four variants co-segregated with the phenotype in these two HSP7 pedigrees.Conclusion:Cerebellar ataxia and cognitive decline might be common in HSP7 patients,compound heterozygous mutations of SPG7 genes were detected in our two HSP7 patients.

关 键 词：遗传性痉挛性截瘫7型 小脑性共济失调 认知功能减退 

分 类 号：R744.9[医药卫生—神经病学与精神病学]