Two novel POLG1 mutations in a patient with progressive external ophthalmoplegia, levodopa-responsive pseudo-orthostatic tremor and parkinsonism
Two novel POLG1 mutations in a patient with progressive external ophthalmoplegia, levodopa-responsive pseudo-orthostatic tremor and parkinsonism
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DOI：
10.1016/j.nmd.2008.04.005
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发表时间：
2008-06-01
影响因子：
2.8
通讯作者：
Zeviani, Massimo
中科院分区：
文献类型：
--
作者：
Invernizzi, Federica;Varanese, Sara;Zeviani, Massimo
POLG1基因编码pol γ A，线粒体DNA聚合酶的催化亚基，不同的突变或突变的组合，与一系列的临床表现，包括常染色体显性或隐性进行性眼外肌麻痹（PEO），青少年发作性共济失调和癫痫，和Alpers-Huttenlocher综合征。据报道，帕金森病特征是POLG1相关显性PEO的晚期并发症。在少数病例中记录了对左旋多巴或多巴胺激动剂的良好反应、纹状体多巴胺摄取减少和黑质背侧部神经元丢失。在这里，我们报告了两个新的突变POLG1在复合杂合子患者与常染色体隐性PEO，其次是假性直立性震颤演变成左旋多巴反应性帕金森病。这些观察结果支持线粒体DNA功能障碍参与特发性帕金森病发病机制的假设。(C)2008 Elsevier B.V.保留所有权利。
Different mutations, or combinations of mutations, in POLG1, the gene encoding pol gamma A, the catalytic subunit of mitochondrial DNA polymerase, are associated with a spectrum of clinical presentations including autosomal dominant or recessive progressive external ophthalmoplegia (PEO), juvenile-onset ataxia and epilepsy, and Alpers-Huttenlocher syndrome. Parkinsonian features have been reported as a late complication of POLG1-associated dominant PEO. Good response to levodopa or dopamine agonists, reduced dopamine uptake in the corpus striatum and neuronal loss of the Substantia Nigra pars compacta have been documented in a few cases. Here we report two novel mutations in POLG1 in a compound heterozygous patient with autosomal recessive PEO, followed by pseudo-orthostatic tremor evolving into levodopa-responsive parkinsonism. These observations support the hypothesis that mtDNA dysfunction is engaged in the pathogenesis of idiopathic Parkinson's disease. (C) 2008 Elsevier B.V. All rights reserved.