Sharp Madeleine E, Marder Karen S, Côté Lucien, Clark Lorraine N, Nichols William C, Vonsattel Jean-Paul, Alcalay Roy N
Department of Neurology, Columbia University, New York, New York, USA.
Mov Disord. 2014 Apr;29(4):566-8. doi: 10.1002/mds.25792. Epub 2013 Dec 27.
PARKIN-related disease remains incompletely understood. First, the pathogenicity of heterozygous PARKIN mutations is unclear, although some evidence supports causality. Second, unlike sporadic Parkinson's disease (PD), Lewy bodies are present only in a minority of cases. Only one other heterozygote PARKIN carrier with autopsy findings has been described. Our case adds to the broadening pathological and clinical phenotype of PARKIN-related disease.
Clinical chart, genetic analysis, and pathological findings of a patient with familial PD are reviewed.
A 44-year-old man developed slowly progressive tremor-predominant PD with excellent response to levodopa. Genetic analysis revealed a heterozygous PARKIN exon 3-4 deletion, also present in 2 family members with early-onset PD. Postmortem examination showed severe neuronal loss in the substantia nigra and nucleus coeruleus with the presence of diffuse Lewy bodies.
The deletion is unlikely an incidental finding considering family history, age at onset, and the presence of clinical and pathological features not typical of sporadic PD.
与帕金蛋白（PARKIN）相关的疾病仍未被完全理解。首先，尽管有一些证据支持因果关系，但杂合性PARKIN突变的致病性尚不清楚。其次，与散发性帕金森病（PD）不同，路易小体仅在少数病例中出现。仅有另外一例有尸检结果的杂合性PARKIN携带者被报道过。我们的病例增加了与PARKIN相关疾病不断扩大的病理和临床表型。
回顾了一名家族性PD患者的临床病历、基因分析和病理结果。
一名44岁男性患以震颤为主的缓慢进展性PD，对左旋多巴反应良好。基因分析显示存在杂合性PARKIN外显子3 - 4缺失，两名早发性PD家族成员也有此缺失。尸检显示黑质和蓝斑有严重神经元丢失，并存在弥漫性路易小体。
考虑到家族史、发病年龄以及存在散发性PD不典型的临床和病理特征，该缺失不太可能是偶然发现。
