An autopsy case of PARK2 due to a homozygous exon 2 deletion of <i>parkin</i> and associated with α‐synucleinopathy
An autopsy case of PARK2 due to a homozygous exon 2 deletion of <i>parkin</i> and associated with α‐synucleinopathy
复制标题
由于 <i>parkin</i> 纯合外显子 2 缺失并与 α-突触核蛋白病相关的 PARK2 尸检病例
DOI：
10.1111/neup.12735
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发表时间：
2021
期刊：
影响因子：
2.3
通讯作者：
Hanajima Ritsuko
中科院分区：
文献类型：
--
作者：
Sakuwa Mayuko;Adachi Tadashi;Yoshida Kentaro;Adachi Yoshiki;Nakano Toshiya;Hanajima Ritsuko
路易小体(Lbs)通常在特发性帕金森病(PD)患者中检测到，但很少有报道Lbs与几个突变相关的家族性早发性PD，parkin是一种编码参与线粒体内稳态的泛素E3连接酶的基因，也被称为PARK2。在此，我们报告一例伴有PARK2突变的帕金森病，其特征是外显子2的纯合缺失和附带的LB病理。一名60岁男子上肢出现震颤。虽然左旋多巴最初是有效的，但他的症状慢慢恶化。他的心肌摄取~(123)I-间碘苯甲基胍，通过心肌核素检查，从发病早期就开始下降。81岁 时，他患上了军团肺炎，死于呼吸衰竭。组织病理学检查显示，黑质和蓝斑有中等程度的色素神经元丢失和胶质细胞增生。在蓝斑、迷走神经背核和Meynert基底核中未见与LB相关的病理改变。心外膜交感神经酪氨酸羟基酶和磷酸化神经丝蛋白免疫反应纤维数量减少。对冰冻脑组织进行的基因分析显示，parkin基因外显子2纯合缺失。据我们所知，这是第一例Parkin外显子2纯合缺失的尸检病例。LBS数目少，发病年龄晚于典型的PARK2相关PD患者，且心脏交感神经支配缺失。因此，我们认为我们的病例中的LBS是偶发性和临床前的α-突触核病症。
Lewy bodies (LBs) are usually detected in patients with idiopathic Parkinson's disease (PD), but there have been few reports of LBs in a familial form of early‐onset PD associated with several mutations inparkin, a gene that encodes a ubiquitin E3 ligase involved in mitochondrial homeostasis, being also known asPARK2. Here, we report a case of PD with aPARK2mutation characterized by a homozygous deletion of exon 2 and incidental LB pathology. A 60‐year‐old man developed tremor in the upper limbs. Although levodopa was initially effective, his symptoms slowly progressed. His cardiac uptake of123I‐metaiodobenzylguanidine, as assessed by myocardial scintigraphy, decreased from an early stage after the onset. At the age of 81 years, he developedLegionellapneumonia and died of respiratory failure. Histopathological examination revealed a moderate loss of pigmented neurons, as well as gliosis in the substantia nigra and the locus coeruleus. Little LB‐related pathology was found in the locus coeruleus, dorsal nucleus of vagal nerve, and basal nucleus of Meynert. The cardiac sympathetic nerve in the epicardium showed a reduction in the numbers of fibers immunoreactive for tyrosine hydroxylase and phosphorylated neurofilament protein. Genetic analysis of frozen brain materials revealed a homozygous deletion of exon 2 ofparkin. To our knowledge, this is the first autopsy case with a homozygous deletion of exon 2 ofparkin. The number of LBs was small, the age of disease onset was later than that in typicalPARK2‐associated PD patients, and cardiac sympathetic denervation was also present. Thus, we considered the LBs in our case as incidental and preclinical α‐synucleinopathy.