Screening for the LRRK2 G2019S and codon-1441 mutations in a pathological series of parkinsonian syndromes and frontotemporal lobar degeneration
Screening for the LRRK2 G2019S and codon-1441 mutations in a pathological series of parkinsonian syndromes and frontotemporal lobar degeneration
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DOI：
10.1016/j.jns.2008.02.010
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发表时间：
2008-07-15
影响因子：
4.4
通讯作者：
Tolosa, Eduardo
中科院分区：
文献类型：
--
作者：
Gaig, Carles;Ezquerra, Mario;Tolosa, Eduardo
背景：与LRRK2突变相关的神经病理是异质性的，但最常见的底物是路易体(LB型)病理。虽然LRRK2突变在帕金森病(PD)中的流行已被广泛研究，但关于LRRK2突变在路易体痴呆(DLB)以及与这些突变相关的其他病理条件中的频率的信息有限，例如无路易体的非特异性黑质变性、tau免疫阳性的神经原纤维缠结病理以及类似于额颞叶变性(FTLD-U)亚型的泛素阳性神经元包涵体。目的：进一步研究与LRRK2突变相关的神经病理学。方法：我们从西班牙一家脑库筛选了110例LRRK2 G2019S和密码子-1441(R141G/C/H)突变其中联核病66例(PD 33例，DLB25例，多系统萎缩8例)，共病29例(进行性核上性瘫痪21例，皮质基底膜变性3例，tau阳性5例)，非特异性黑质变性3例，tau阴性FTLD 12例(9例FTLD-U和3例缺乏明确组织学特征的痴呆)。结果：发现2例G2019S突变：1例经临床和病理诊断为PD，1例为典型PD，神经病理检查发现非特异性黑质变性。在另一例帕金森病患者中发现了一个同义突变(R1441R；c.4323C>；T)。结论：在这个基于脑库的序列中，LRRK2 G2019S突变发生在帕金森病合并典型脑干LB病理或非特异性黑质变性的患者中。LRRK2突变在其他与突触核蛋白和tau沉积相关的神经退行性疾病中未见。(C)2008爱思唯尔B.V.保留所有权利。
Background: The neuropathology associated with LRRK2 mutations is heterogeneous but Lewy body (LB) type pathology is the most common substrate encountered. While the prevalence of LRRK2 mutations has been extensively studied in Parkinson's disease (PD), limited information is available on the frequency of LRRK2 mutations in dementia with Lewy bodies (DLB) and in other pathological conditions associated with these mutations, such as non-specific nigral degeneration without LB, tau-immunopositive neurofibrillary tangle pathology, and ubiquitin-positive neuronal inclusions resembling those observed in a subtype of frontotemporal lobar degeneration (FTLD-U).Objective: To further investigate the neuropathology associated with LRRK2 mutations.Methods: We have screened for the LRRK2 G2019S and codon-1441 (R1441G/C/H) mutations in 110 cases from a Spanish Brain Bank, which include: 66 synucleinopathies (33 PD, 25 DLB and 8 multiple system atrophy cases), 29 tauopathies (21 progressive supranuclear palsy, 3 corticobasal degeneration and 5 tau-positive FTLD cases), 3 cases of non-specific nigral degeneration and 12 tau-negative FTLD (9 FTLD-U and 3 dementia lacking distinctive histology cases).Results: The G2019S mutation was found in two cases: One case had a clinical and pathological diagnosis of PD and the other suffered from typical PD and on neuropathological examination had non-specific nigral degeneration without LB. A synonymous variant (R1441R; c.4323C > T) was detected in another PD case.Conclusions: In this brain bank-based series, LRRK2 G2019S mutation occurred in patients with parkinsonism associated with either typical brainstem LB pathology or non-specific nigral degeneration. LRRK2 mutations were not encountered in other neurodegenerative disorders associated with synuclein and tau deposition. (c) 2008 Elsevier B.V. All rights reserved.