Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease
Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease
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DOI：
10.1016/j.neuron.2004.10.023
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发表时间：
2004-11-18
期刊：
影响因子：
16.2
通讯作者：
Singleton, AB
中科院分区：
文献类型：
--
作者：
Paisán-Ruíz, C;Jain, S;Singleton, AB
帕金森病（PD；OMIM #168600）是西方世界第二常见的神经退行性疾病，表现为进行性运动障碍。 PD 的标志性病理特征是黑质和神经元细胞内路易体包涵体的多巴胺能神经元丧失。帕金森症通常是散发性的。然而，几种罕见的家族形式与基因位点有关，并且因果突变的识别提供了对疾病过程的深入了解。 Funayama 及其同事于 2002 年发现的 PARK8 似乎是家族性 PD 的常见原因。我们在此描述了在来自英格兰和西班牙的五个家族中克隆了一种新基因，该基因包含与 PARK8 相关的 PD 分离的错义突变。由于在 PD 中观察到震颤，并且由于许多家族具有巴斯克血统，我们将这种蛋白质命名为 dardarin，源自巴斯克语单词 dardara，意思是震颤。
Parkinson's disease (PD; OMIM #168600) is the second most common neurodegenerative disorder in the Western world and presents as a progressive movement disorder. The hallmark pathological features of PD are loss of dopaminergic neurons from the substantia nigra and neuronal intracellular Lewy body inclusions. Parkinsonism is typically sporadic in nature; however, several rare familial forms are linked to genetic loci, and the identification of causal mutations has provided insight into the disease process. PARK8, identified in 2002 by Funayama and colleagues, appears to be a common cause of familial PD. We describe here the cloning of a novel gene that contains missense mutations segregating with PARK8-linked PD in five families from England and Spain. Because of the tremor observed in PD and because a number of the families are of Basque descent, we have named this protein dardarin, derived from the Basque word dardara, meaning tremor.