Department of Medicine (Neurology), Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
Mov Disord. 2013 Jun;28(6):811-3. doi: 10.1002/mds.25421. Epub 2013 Mar 1.
Alpha-synuclein plays a central role in the pathophysiology of Parkinson's disease. Three missense mutations in SNCA, the gene encoding alpha-synuclein, as well as genomic multiplications have been identified as causes for autosomal-dominantly inherited Parkinsonism.
Here, we describe a novel missense mutation in exon 4 of SNCA encoding a H50Q substitution in a patient with dopa-responsive Parkinson's disease with a family history of parkinsonism and dementia.
The variant was not observed in public databases or identified in unrelated subjects.
The substitution's evolutionary conservation and protein modeling provide additional support for pathogenicity as the amino acid perturbs the same amphipathic alpha helical structure as the previously described pathogenic mutations.
α-突触核蛋白在帕金森病的病理生理学中起核心作用。SNCA 基因（编码α-突触核蛋白）的三个错义突变以及基因组的多次倍增已被确定为常染色体显性遗传帕金森病的原因。
在这里，我们描述了一位具有家族性帕金森病和痴呆病史的多巴反应性帕金森病患者的 SNCA 外显子 4 中的一个新错义突变，该突变导致 H50Q 取代。
该变体未在公共数据库中观察到，也未在无关个体中发现。
该取代的进化保守性和蛋白质建模为其致病性提供了额外的支持，因为该氨基酸会扰乱与先前描述的致病性突变相同的两亲性α螺旋结构。
