PLA2G6相关帕金森综合征6例临床与遗传学特点并文献复习  

PLA2G6-related parkinsonism:clinical and genetic characteristics of 6 cases and literature review

作　　者：谢曼青[1] 袁晶[1] 郝红琳[1] 毛晨晖[1] 戴毅[1] 郭毅[2] 王含[1] 万新华[1] Xie Manqing;Yuan Jing;Hao Honglin;Mao Chenhui;Dai Yi;Guo Yi;Wang Han;Wan Xinhua(Department of Neurology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,Beijing 100730,China;Department of Neurosurgery,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医院神经科,北京100730 [2]中国医学科学院北京协和医院神经外科,北京100730

出　　处：《中华神经科杂志》2023年第12期1389-1397,共9页Chinese Journal of Neurology

基　　金：国家自然科学基金面上项目(82171255)。

摘　　要：目的探讨PLA2G6相关帕金森综合征患者的临床特点及基因变异特征。方法回顾性收集2015年1月至2022年12月在北京协和医院神经科住院的6例PLA2G6相关帕金森综合征病例,总结其临床、影像学及基因型特点,并进行电话随访。结果在6例患者中,男女各3例,起病年龄为(24.3±5.4)岁。5例临床表型为肌张力障碍-帕金森综合征(DP),头颅磁共振成像(MRI)均存在明显脑萎缩;1例临床表型为早发型帕金森病(EOPD),头颅MRI未发现明显结构异常。仅1例患者可见颅内异常铁沉积。6例患者均对左旋多巴制剂治疗有效。3例患者完善左旋多巴负荷试验,结果示统一帕金森病评定量表第三部分(UPDRS-Ⅲ)评分的最大改善率分别为10.3%(DP表型)、10.6%(DP表型)和77.0%(EOPD表型)。4例患者在左旋多巴制剂应用1年内出现异动症。2例患者分别行双侧丘脑底核-脑深部电刺激(DBS)术和苍白球内侧-DBS术,术后临床获益均不显著。6例患者中共发现8种PLA2G6基因突变类型,其中有2个为新突变,分别为c.1973A>G杂合突变和外显子2的杂合缺失突变,根据美国医学遗传学和基因组学学会指南,分别可评级为疑似致病变异和致病变异。4例患者存在c.991G>T杂合突变。结论PLA2G6相关早发型帕金森综合征临床表型复杂,影像学常见小脑萎缩,多巴胺能药物疗效EOPD型优于DP型,DP型患者伴明显脑萎缩者DBS手术疗效可能欠佳。c.991G>T为其常见的突变位点,存在奠基者效应可能。Objective To elucidate the clinical and genetic characteristics of PLA2G6-related parkinsonism.Methods The clinical,imaging and genetic data of 6 patients with PLA2G6-related parkinsonism admitted to Peking Union Medical College Hospital from January 2015 to December 2022 were retrospectively collected and analyzed.The prognosis was followed up through phone call.Results There were 3 male and 3 female patients,and the age of disease onset was(24.3±5.4)years.Phenotypically,5 of them had dystonia-parkinsonism(DP)with obvious atrophy of cerebellum and 1 presented as early-onset Parkinson′s disease(EOPD)with no brain structural abnormality.Only 1 patient presented with abnormal brain iron deposition.All of the patients were partially responsive to levodopa.Three cases underwent levodopa challenge test with the objective levodopa responsiveness varied from 10.3%and 10.6%in 2 DP patients,to 77.0%in 1 EOPD patient.Levodopa-induced dyskinesias were present in 4 of them,and all appeared within the first year since the initiation of dopaminergic treatment.Two patients underwent bilateral deep brain stimulation(DBS)of subthalamic nucleus and globus pallidus internus respectively,albeit revealed poor outcome.Genetically,8 PLA2G6 variants were identified.Two of them were found to be novel(c.1973A>G and exon2 heterozygous deletion),and the most frequent variant was the c.991G>T mutation which was detected in 4 patients.Conclusions The phenotype of PLA2G6-related parkinsonism is complex.Cerebellar atrophy is a frequent magnetic resonance imaging feature.Levodopa responsiveness tends to depend on the clinical phenotype,and EOPD is better than DP.DBS might not be promising in DP patients with obvious cerebral atrophy.The c.991G>T mutation is the most frequent mutation,suggesting a common founder effect.

关 键 词：帕金森综合征 PLA2G6基因 脑组织铁沉积神经变性病 脑深部电刺激术 

分 类 号：R742.5[医药卫生—神经病学与精神病学]