Importance of familial Parkinson's disease and parkinsonism to the understanding of nigral degeneration in sporadic Parkinson's disease.
Importance of familial Parkinson's disease and parkinsonism to the understanding of nigral degeneration in sporadic Parkinson's disease.
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家族性帕金森病和帕金森病对于了解散发性帕金森病黑质变性的重要性。
DOI：
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Y. Mizuno
中科院分区：
文献类型：
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作者：
N. Hattori;H. Shimura;S. Kubo;M. Wang;N. Shimizu;K. Tanaka;Y. Mizuno
本文就家族性帕金森病的临床及分子遗传学方面的研究进展作一综述。遗传因素对帕金森病发病机制的贡献得到了双胞胎高一致性的证明，病例对照和家族研究中帕金森病患者亲属的风险增加，以及基于单基因缺陷的家族性帕金森病和帕金森综合征的存在。最近，一些基因已被映射和/或确定在家族性PD患者。α-突触核蛋白参与了一种罕见的显性形式的家族性PD，具有多巴反应性帕金森病特征和路易体阳性病理学。相比之下，帕金是负责常染色体隐性形式的早发性PD与路易体阴性病理。这种形式在全球范围内的复发性PD患者中发现。此外，泛素羧基末端水解酶L1基因是一种常染色体显性形式的典型PD的原因，尽管迄今为止只有一个家族被鉴定出具有该基因的突变，并且tau已被鉴定为额颞叶痴呆和帕金森综合征的致病基因。此外，其他五个染色体位点已被确定与家族性PD或肌张力障碍-帕金森综合征。不同位点或不同致病基因的存在表明PD不是一个单一的实体，而是高度异质性的。致病基因的鉴定和阐明将有助于我们对散发性PD发病机制的理解。
We review here familial Parkinson's disease (PD) from clinical as well as molecular genetic aspects. The contribution of genetic factors to the pathogenesis of PD is supported by the demonstration of the high concordance in twins, increased risk among relatives of PD patients in case control and family studies, and the existence of familial PD and parkinsonism based on single gene defects. Recently, several genes have been mapped and/or identified in patients with familial PD. Alpha-synuclein is involved in a rare dominant form of familial PD with dopa responsive parkinsonian features and Lewy body positive pathology. In contrast, parkin is responsible for autosomal recessive form of early-onset PD with Lewy body-negative pathology. This form is identified world-wide among patients with young-onset PD. Furthermore, ubiquitin carboxy terminal hydrolase L1 gene is responsible for an autosomal dominant form of typical PD, although only a single family has so far been identified with a mutation of this gene, and tau has been identified as a causative gene for frontotemporal dementia and parkinsonism. In addition, five other chromosome loci have been identified to be linked to familial PD or dystonia-parkinsonism. The presence of different loci or different causative genes indicates that PD is not a single entity but a highly heterogeneous. Identification and elucidation of the causative genes should enhance our understanding of the pathogenesis of sporadic PD.
影响因子：
56.9
作者：
Masliah, E;Rockenstein, E;Mucke, L
通讯作者：
Mucke, L
影响因子：
2.9
作者：
Larsen, CN;Krantz, BA;Wilkinson, KD
通讯作者：
Wilkinson, KD