Global investigation and meta-analysis of the C9orf72 (G4C2)n repeat in Parkinson disease.
Global investigation and meta-analysis of the C9orf72 (G4C2)n repeat in Parkinson disease.
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DOI：
10.1212/wnl.0000000000001012
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发表时间：
2014-11-18
期刊：
影响因子：
9.9
通讯作者：
GEO-PD Consortium
中科院分区：
文献类型：
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作者：
Theuns J;Verstraeten A;Sleegers K;Wauters E;Gijselinck I;Smolders S;Crosiers D;Corsmit E;Elinck E;Sharma M;Krüger R;Lesage S;Brice A;Chung SJ;Kim MJ;Kim YJ;Ross OA;Wszolek ZK;Rogaeva E;Xi Z;Lang AE;Klein C;Weissbach A;Mellick GD;Silburn PA;Hadjigeorgiou GM;Dardiotis E;Hattori N;Ogaki K;Tan EK;Zhao Y;Aasly J;Valente EM;Petrucci S;Annesi G;Quattrone A;Ferrarese C;Brighina L;Deutschländer A;Puschmann A;Nilsson C;Garraux G;LeDoux MS;Pfeiffer RF;Boczarska-Jedynak M;Opala G;Maraganore DM;Engelborghs S;De Deyn PP;Cras P;Cruts M;Van Broeckhoven C;GEO-PD Consortium
本研究的目的是在全球帕金森病多中心遗传流行病学(GEO-PD)队列中阐明(G4C2)n扩展在帕金森病(PD)病因学中的作用。在欧洲、亚洲、北美和澳大利亚确诊的7,494名帕金森病患者和5,886名神经健康对照患者中，对GEO-PD队列中的C9ORF72(G4C2)n重复进行了评估。仅4例帕金森病患者(4/7,232；0.055%)检测到致病性(G4C2)N>；60扩增，均有神经退行性痴呆、肌萎缩侧索硬化症或不典型帕金森病家族史，未发现典型的散发性或家族性帕金森病携带者。Meta分析显示，随着(G4C2)n重复数的增加，患帕金森病的风险略有增加；然而，我们没有发现C9orf72(G4C2)n重复与帕金森病之间存在明显的关联，而且人群归因风险很低。综上所述，这些发现表明C9orf72的扩张在帕金森病的发病机制中没有主要作用。C9orf72重复扩增检测仅适用于有明显额颞叶变性/肌萎缩侧索硬化症症状或有明显神经退行性痴呆或运动神经元病家族史的帕金森病患者。
The objective of this study is to clarify the role of (G4C2)n expansions in the etiology of Parkinson disease (PD) in the worldwide multicenter Genetic Epidemiology of Parkinson's Disease (GEO-PD) cohort. C9orf72 (G4C2)n repeats were assessed in a GEO-PD cohort of 7,494 patients diagnosed with PD and 5,886 neurologically healthy control individuals ascertained in Europe, Asia, North America, and Australia. A pathogenic (G4C2)n>60 expansion was detected in only 4 patients with PD (4/7,232; 0.055%), all with a positive family history of neurodegenerative dementia, amyotrophic lateral sclerosis, or atypical parkinsonism, while no carriers were detected with typical sporadic or familial PD. Meta-analysis revealed a small increase in risk of PD with an increasing number of (G4C2)n repeats; however, we could not detect a robust association between the C9orf72 (G4C2)n repeat and PD, and the population attributable risk was low. Together, these findings indicate that expansions in C9orf72 do not have a major role in the pathogenesis of PD. Testing for C9orf72 repeat expansions should only be considered in patients with PD who have overt symptoms of frontotemporal lobar degeneration/amyotrophic lateral sclerosis or apparent family history of neurodegenerative dementia or motor neuron disease.