Parkin disease: a clinicopathologic entity?
Parkin disease: a clinicopathologic entity?
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帕金氏病：临床病理学实体？
DOI：
10.1001/jamaneurol.2013.172
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发表时间：
2013-05
期刊：
影响因子：
29
通讯作者：
Holton, Janice L.
中科院分区：
文献类型：
--
作者：
Doherty, Karen M.;Silveira-Moriyama, Laura;Parkkinen, Laura;Healy, Daniel G.;Farrell, Michael;Mencacci, Niccolo E.;Ahmed, Zeshan;Brett, Francesca M.;Hardy, John;Quinn, Niall;Counihan, Timothy J.;Lynch, Timothy;Fox, Zoe V.;Revesz, Tamas;Lees, Andrew J.;Holton, Janice L.
Parkin 编码基因 (PARK2) 突变是常染色体隐性遗传青少年发病和年轻发病帕金森病的最常见原因。少数可用的详细神经病理学报告表明，纯合和复合杂合 Parkin 突变的特征是严重的黑质致密部神经元损失。探讨帕金相关帕金森症是否是与帕金森病 (PD) 不同的临床病理实体。我们描述了 5 例无关的帕金病病例的临床、遗传和神经病理学发现，并将其与 5 例病理证实的帕金森病病例和 4 例对照受试者进行比较。 PD对照病例和正常对照受试者首先匹配死亡年龄，然后匹配疾病持续时间（仅PD）以进行比较。帕金病病例的症状是手或腿震颤，通常伴有肌张力障碍。平均发病年龄为 34 岁；所有病例均为parkin突变复合杂合子。步态冻结、姿势畸形和运动波动是常见的晚期特征。没有患者有任何认知障碍或痴呆的证据。黑质致密部的神经元计数显示，parkin 病例中的神经元损失与 PD 中的神经元损失一样严重，但与 PD 相比，背侧层的相对保留（P = .04）。在蓝斑和迷走神经背运动核中发现了轻度神经元损失，但在迈纳特基底核、中缝核或其他脑区域中没有发现。 2 例（脑干和皮质）发现稀疏路易体。这些发现支持这样的观点，即帕金病的特征是比帕金森病更有限的形态异常，主要是腹侧黑质变性，路易体缺失或罕见。
Mutations in the gene encoding parkin (PARK2) are the most common cause of autosomal recessive juvenile-onset and young-onset parkinsonism. The few available detailed neuropathologic reports suggest that homozygous and compound heterozygous parkin mutations are characterized by severe substantia nigra pars compacta neuronal loss. To investigate whether parkin -linked parkinsonism is a different clinicopathologic entity to Parkinson disease (PD). We describe the clinical, genetic, and neuropathologic findings of 5 unrelated cases of parkin disease and compare them with 5 pathologically confirmed PD cases and 4 control subjects. The PD control cases and normal control subjects were matched first for age at death then disease duration (PD only) for comparison. Presenting signs in the parkin disease cases were hand or leg tremor often combined with dystonia. Mean age at onset was 34 years; all cases were compound heterozygous for mutations of parkin. Freezing of gait, postural deformity, and motor fluctuations were common late features. No patients had any evidence of cognitive impairment or dementia. Neuronal counts in the substantia nigra pars compacta revealed that neuronal loss in the parkin cases was as severe as that seen in PD, but relative preservation of the dorsal tier was seen in comparison with PD (P = .04). Mild neuronal loss was identified in the locus coeruleus and dorsal motor nucleus of the vagus, but not in the nucleus basalis of Meynert, raphe nucleus, or other brain regions. Sparse Lewy bodies were identified in 2 cases (brainstem and cortex). These findings support the notion that parkin disease is characterized by a more restricted morphologic abnormality than is found in PD, with predominantly ventral nigral degeneration and absent or rare Lewy bodies.
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DOI：
10.1016/j.bbamcr.2010.08.007
发表时间：
2011-04
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Deas E;Wood NW;Plun-Favreau H
通讯作者：
Plun-Favreau H
影响因子：
3.5
作者：
Cookson, MR;Lockhart, PJ;Farrer, MJ
通讯作者：
Farrer, MJ
影响因子：
14.5
作者：
Khan, NL;Brooks, DJ;Piccini, P
通讯作者：
Piccini, P
影响因子：
4.8
作者：
Hristova, Ventzislava A.;Beasley, Steven A.;Shaw, Gary S.
通讯作者：
Shaw, Gary S.
影响因子：
8.6
作者：
Miyakawa, Saori;Ogino, Mieko;Mochizuki, Hideki
通讯作者：
Mochizuki, Hideki