Reta Lila Weston Institute for Neurological Studies, University College London, London, England.
JAMA Neurol. 2013 May;70(5):571-9. doi: 10.1001/jamaneurol.2013.172.
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).
DESIGN, SETTING, AND PARTICIPANTS: 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.
编码 parkin（PARK2）的基因突变是常染色体隐性遗传少年型和青年型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丧失。
研究 parkin 相关帕金森病是否与帕金森病（PD）存在不同的临床病理实体。
设计、地点和参与者：我们描述了 5 例 parkin 病的临床、遗传和神经病理学发现，并将其与 5 例经病理证实的 PD 病例和 4 例对照进行了比较。PD 对照组病例和正常对照组首先根据死亡年龄进行匹配，然后根据疾病持续时间（仅 PD）进行匹配，以进行比较。
parkin 病病例的首发症状是手部或腿部震颤，常伴有肌张力障碍。发病年龄的平均值为 34 岁；所有病例均为 parkin 基因突变的复合杂合子。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 病例的神经元丧失与 PD 一样严重，但与 PD 相比，背层相对保留（P =.04）。蓝斑和迷走神经背核中发现轻度神经元丧失，但核基底节、中缝核或其他脑区没有。在 2 例（脑干和皮质）中发现稀疏的 Lewy 体。
这些发现支持这样一种观点，即 parkin 病的特征是形态异常比 PD 更局限，主要是腹侧黑质变性，缺乏或罕见 Lewy 体。
