PRKN基因突变所致早发型帕金森病家系的临床特征及基因检测  

Clinical Characteristics and Genetic Testing of A Pedigree with Early-onset Parkinson's Disease Caused by PRKN Gene Mutation

作　　者：廖书胜 陈红[1] 刘玫 潘成玉 罗瑷涤 张丽 LIAO Shusheng;CHEN Hong;LIU Mei;PAN Chengyu;LUO Aidi;ZHANG Li(Dept.of Neurology,Liuzhou People’s Hospital Affiliated to Guangxi Medical University,Liuzhou Guangxi 545006;Dept.of Neurology,The Affiliated Hospital of Zunyi Medical University,Zunyi Guizhou 563003,China)

机构地区：[1]广西医科大学附属柳州市人民医院神经内科,广西柳州545006 [2]遵义医科大学附属医院神经内科,贵州遵义563003

出　　处：《昆明医科大学学报》2023年第5期66-71,共6页Journal of Kunming Medical University

基　　金：国家自然科学基金资助项目(82160316,81260177);贵州省科技厅自然科学基金资助项目[黔科合基础(2019)1351号]。

摘　　要：目的 探讨2个常染色体隐性遗传早发型帕金森病(autosomal recessive early-onset parkinsonism,AREP)家系中2名患者的临床特征及基因突变情况。方法 对2个中国汉族家庭中共2名患者进行临床资料的收集和基因突变分析。使用靶区捕获和高通量测序筛选与帕金森病(Parkinson’s disease,PD)、震颤、脊髓小脑性共济失调和肌张力障碍等疾病相关的基因;应用多重连接依赖探针扩增(multiples ligation-dependent probe amplification,MLPA)法检测SNCA、LRRK2、PARK2、PINK1、PARK7、ATP13A2、UCHL1、GCH1等基因外显子的重排和大缺失突变。结果 2名临床确诊为PD的患者表现出明显的临床及遗传异质性。基因检测发现家系1的患者存在PRKN基因2号外显子杂合缺失变异和c.619G> T/p.Glu207Ter*杂合变异2种突变,该复合杂合变异与疾病存在家系共分离。家系2的患者存在PRKN基因3~4号外显子纯合缺失变异,且存在LRRK2基因c.4827+6T> A杂合变异及PINK1基因c.1474C> T/p.Arg492*杂合变异;生物信息学分析发现LRRK2基因的c.4827+6T> A变异可能导致其剪切改变。结论 PRKN基因突变所致的早发型帕金森病临床表现及基因突变形式多样;AREP患者可能同时存在多个PD基因致病突变,且其临床发病年龄更早,症状更重更复杂,病情进展更快。Objective To investigate the clinical characteristics and gene mutations of 2 patients in 2 families of autosomal recessive early-onset Parkinson’s disease(AREP).Methods Clinical data and gene mutation analysis were performed on 2 patients from 2 Chinese Han families.Target capture and high-throughput sequencing were used to screen genes related to Parkinson’s disease(PD),tremor,spinocerebellar ataxia,and dystonia;Multiple ligation-dependent probe amplification(MLPA)was used to detect the rearrangement and large deletion mutations of SNCA,LRRK2,PARK2,PINK1,PARK7,ATP13A2,UCHL1,GCH1 gene exons.Results 2 patients with clinically confirmed PD showed the obvious clinical and genetic heterogeneity.Gene detection found that there were two mutations in the PRKN gene exon 2 heterozygous deletion mutation and c.619G>T/p.Glu207Ter*heterozygous mutation in the patient of family 1.The compound heterozygous mutation was pedigree cosegregated in the family.The patients of pedigree 2 had homozygous deletion mutation in exon 3-4 of PRKN gene,and had heterozygous mutation in LRRK2 gene c.4827+6T>A,and heterozygous mutation in PINK1 gene c.1474C>T/p.Arg492*;Bioinformatics analysis found that the c.4827+6T>A mutation of LRRK2 gene may lead to its shear change.Conclusion The clinical manifestations and gene mutations of early-onset Parkinson’s disease caused by PRKN gene mutations are diverse;AREP patients may have multiple PD gene pathogenic mutations at the same time,and their clinical onset age is earlier,the symptoms are more severe and complex,and the disease progresses are faster.

关 键 词：早发型帕金森病 PRKN基因 LRRK2基因 PINK1基因 

分 类 号：R446.9[医药卫生—诊断学]