A Peruvian family with a novel PARK2 mutation: Clinical and pathological characteristics
A Peruvian family with a novel PARK2 mutation: Clinical and pathological characteristics
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DOI：
10.1016/j.parkreldis.2015.01.005
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发表时间：
2015-05-01
影响因子：
4.1
通讯作者：
Leverenz, James B.
中科院分区：
文献类型：
--
作者：
Cornejo-Olivas, Mario R.;Torres, Luis;Leverenz, James B.
背景：PARK2基因突变导致常染色体隐性遗传性青年帕金森病(YOPD)。虽然已经有一些关于PARK2相关帕金森病的临床特征的报道，但关于相关的神经病理改变的信息有限。设计：我们描述了一个患有YOPD的秘鲁家庭的临床和病理特征。对先证者和一个未受影响的同胞进行PARK2剂量和点突变筛查。一个受影响的兄弟姐妹进行了详细的神经病理检查。单位：秘鲁利马的国家神经病学研究所(IncN)。结果：先证者及其四个兄弟姐妹中的两个患上了YOPD，父母均未受影响。临床病程的特点是僵硬性帕金森病，主要累及下肢和运动障碍。PARK2分析表明，先证者是第5内含子新的受体剪接点突变(IVS5-1G>；A)和外显子7缺失的复合杂合子。对一个受影响的兄弟姐妹进行的神经病理学评估显示，黑质(SN)有严重的神经元丢失，纹状体有酪氨酸羟基酶免疫阳性纤维的丢失。结论：与大多数PARK2突变患者的神经病理学报告一致，我们没有观察到路易体包涵体，尽管纹状体有明显的黑质变性和严重的多巴胺能神经失神经。这些数据描述了一种新的剪接点突变，并进一步扩展了PARK2相关PD的临床病理特征。(C)2015爱思唯尔有限公司。保留所有权利。
Background: Mutations in PARK2 result in autosomal recessive young onset Parkinson's disease (YOPD). Although there have been a number of reports on the clinical characteristics of PARK2-related PD, there is limited information available on the associated neuropathologic changes.Design: We describe the clinical and pathological characteristics of a Peruvian family with YOPD. The proband and one unaffected sibling were screened for PARK2 dosage and point mutations. One affected sibling had detailed neuropathologic examination.Setting: Instituto Nacional de Ciencias Neurologicas (INCN) in Lima, Peru.Results: The proband and two of her four siblings developed YOPD and both parents were unaffected. The clinical course has been characterized by akinetic-rigid parkinsonism predominantly affecting the lower limbs and dyskinesias. Analysis of PARK2 showed that the proband is compound heterozygous for a novel acceptor splice site mutation in intron 5 (IVS5-1G>A) and an exon 7 deletion. Neuropathologic assessment of an affected sibling revealed severe neuronal loss in the substantia nigra (SN) and loss of tyrosine hydroxylase immunopositive fibers in the striatum. No Lewy body pathology was observed using standard histology or immunohistochemistry for alpha-synuclein.Conclusions: Consistent with most neuropathologic reports of patients with PARK2 mutations, we did not observe Lewy body inclusions, despite marked SN degeneration and severe dopaminergic denervation of the striatum. These data describe a novel splice site mutation and further extend the clinicopathological characterization of PARK2-associated PD. (C) 2015 Elsevier Ltd. All rights reserved.