一个肌张力障碍-帕金森综合征的家系调查及致病基因研究  

Investigation and genetic study on a pedigree of dystonia-parkinsonism

作　　者：高晨雨 黄婷 陈睿[1] 刘春梅[1] 张颖冬[1] 田有勇[1] GAO Chen-yu;HUANG Ting;CHEN Rui(Department of Neurology,Nanjing-First Hospital AJfiliated to Nanjin Medical University,210006 Nanjing,China)

机构地区：[1]南京医科大学附属南京医院(南京市第一医院)神经内科,210006

出　　处：《临床神经病学杂志》2020年第6期416-420,共5页Journal of Clinical Neurology

基　　金：江苏省临床医学科技重大专项(BL2014014)。

摘　　要：目的初步分析一个肌张力障碍-帕金森综合征家系的可能致病基因。方法对一个肌张力障碍-帕金森综合征的家系进行家系调查。在收集先证者相关血液生化指标、超声波、MRI影像学和PET核医学检查等临床资料基础上,对先证者及其家系三代共8人先后进行了目标基因以及全外显子基因测序加可疑位点Sanger测序验证。结果先证者临床表现为眼睑、口面、下肢肌张力异常,伴动作慢、肌张力高和震颤等典型肌张力障碍-帕金森综合征症状,多巴胺能药物不敏感及服药后罕见的阴道出血不良反应。血生化、铜蓝蛋白、肝脏超声及角膜裂隙灯照相、头颈及腰段脊髓MRI扫描均正常,头颅18F-dopa PET/MRI显像提示双侧豆状核多巴胺神经元受损。该家系三代共9人中出现症状2例(1例已死亡),基因检测显示先证者及另外3人携带父源的RYR1基因36号外显子c.5972C>T(p.T1911I)杂合突变;另有SETX基因外显子10的c.2439A>C(p.E813D)杂合突变;GCDH基因外显子10的c.1060G>A(p.G354S)杂合突变;ATP7B基因外显子18的c.3792G>C(p.M1264I)杂合突变;上述突变致病意义均未明确。结论本研究未找到已报道的肌张力障碍-帕金森综合征家系相关基因突变,其致病基因需进一步探讨。Objective To analyze possible pathogenic genes in a pedigree of dystonia-parkinsonism.MethodsA family investigation of a pedigree of dystonia-parkinsonism was conducted.Blood biochemical index,ultrasound,MRI,and PET/MRI were performed on the proband.Eight subjects from three generations of the family were sequenced by target region sequencing and whole-exome sequencing.Sanger sequencing was used to verify the suspicious alternations.Results The proband had typical dystonia-parkinsonian symptoms including blepharospasm,oromandibular dystonia,and lower limb dystonia,accompanied with bradykinesia,tremor,and rigidity.Dopaminergic drug had no therapeutic effect in the proband but present a rare side effect of vaginal bleeding.Blood biochemical index,ceruloplasmin,liver ultrasound,digital slit-lamp photography,and brain MRI scan were normal.Brain 18F-dopa PET/MRI scan indicated reduced signal in lenticular nucleus.Clinical symptoms were observed in two persons(one deceased)of nine subjects from three generation of the family.The proband and three other members of the family were detected a heterozygous mutation c.5972 C>T(p.T1911 I)in exon 36 of RYR1,inherited from father.Besides,heterozygous mutations c.2439 A>C(p.E813 D)in exon 10 of SETX,c.1060 G>A(p.G354 S)in exon10 of GCDH,and c.3792 G>C(p.M1264 I)in exon 18 of ATP7B were carried by the proband.The pathogenicity of these mutations was not clear.Conclusions Genetic evaluation of the family failed to reveal a reported etiology associated with dystonia-parkinsonism.Its pathogenic genes are worth further study.

关 键 词：肌张力障碍-帕金森综合征 全外显子测序 家系调查 

分 类 号：R742.5[医药卫生—神经病学与精神病学]