Alpha-synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease
Alpha-synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease
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DOI：
10.1002/mds.25421
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发表时间：
2013-06-01
影响因子：
8.6
通讯作者：
Farrer, Matthew J.
中科院分区：
文献类型：
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作者：
Appel-Cresswell, Silke;Vilarino-Guell, Carles;Farrer, Matthew J.
研究背景α-突触核蛋白在帕金森病的病理生理学中起着重要作用。编码α-突触核蛋白的基因SNCA中的三个错义突变以及基因组倍增已被确定为常染色体显性遗传性帕金森病的原因。方法在这里，我们描述了一个新的错义突变SNCA外显子4编码H50 Q取代与多巴反应性帕金森氏病患者的帕金森氏症和痴呆的家族史。结果在公共数据库中未发现该变异，在无关受试者中也未发现该变异。结论取代的进化保守性和蛋白质建模为致病性提供了额外的支持，因为氨基酸扰乱了与先前描述的致病性突变相同的两亲性α螺旋结构。(c)2013年运动障碍协会
Background 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. Methods 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. Results The variant was not observed in public databases or identified in unrelated subjects. Conclusions 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. (c) 2013 Movement Disorder Society