帕金基因及其表型。意大利帕金森病遗传学研究小组、法国帕金森病遗传学研究小组以及帕金森病遗传易感性欧洲联盟。

The parkin gene and its phenotype. Italian PD Genetics Study Group, French PD Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease.

作者信息

Bonifati V, De Michele G, Lücking C B, Dürr A, Fabrizio E, Ambrosio G, Vanacore N, De Mari M, Marconi R, Capus L, Breteler M M, Gasser T, Oostra B, Wood N, Agid Y, Filla A, Meco G, Brice A

机构信息

Department of Neurological Sciences, La Sapienza University, Rome, Italy.

出版信息

Neurol Sci. 2001 Feb;22(1):51-2. doi: 10.1007/s100720170042.

DOI:10.1007/s100720170042

PMID:11487197

Abstract

Mutations of the parkin gene on chromosome 6 cause autosomal recessive, early onset parkinsonism. This is the most frequent form of monogenic parkinsonism so far identified. The associated phenotypical spectrum encompasses early onset, levodopa-responsive parkinsonism (average onset in the early 30s in Europe), and it overlaps with dopa-responsive dystonia in cases with the earliest onset, and with clinically typical Parkinson's disease in cases with later onset. Despite clinical features, Lewy bodies are not found at autopsy in brains of patients with parkin mutations. The parkin protein possesses ubiquitin ligase activity, which is abolished by the pathogenic mutations.

摘要

6号染色体上的帕金森基因（parkin gene）突变会导致常染色体隐性遗传的早发性帕金森症。这是目前已确定的最常见的单基因帕金森症形式。其相关的表型谱包括早发性、左旋多巴反应性帕金森症（在欧洲平均发病年龄为30岁出头），在发病最早的病例中与多巴反应性肌张力障碍重叠，在发病较晚的病例中与临床典型的帕金森病重叠。尽管有这些临床特征，但在患有帕金森基因突变的患者大脑尸检中未发现路易小体。帕金森蛋白具有泛素连接酶活性，而这种活性会被致病性突变所消除。