Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
Neurobiol Aging. 2012 Aug;33(8):1844.e11-3. doi: 10.1016/j.neurobiolaging.2012.01.006. Epub 2012 Feb 14.
VPS35 was recently identified as a novel autosomal dominant gene for Parkinson disease. In this study, we aimed to determine the contribution of simple and complex VPS35 variations to the genetic etiology of the spectrum of Lewy body disorders (LBD) in a Flanders-Belgian patient cohort (n = 677). We identified 3 novel missense variations in addition to 1 silent and 1 intronic variation predicted to activate a cryptic splice site, but no copy number variations. Despite the absence of these rare variations in the control group (n = 800), we could not attain convincing evidence for pathogenicity by segregation analysis or in silico predictions. Hence, our data do not support a major role for VPS35 variations in the genetic etiology of Lewy body disorders in the Flanders-Belgian population.
VPS35 最近被确定为一种新的常染色体显性基因,与帕金森病有关。在这项研究中,我们旨在确定简单和复杂的 VPS35 变异对弗拉芒-比利时患者队列(n = 677)中路易体障碍(LBD)谱遗传病因的贡献。除了 1 个预测激活隐性剪接位点的无意义和 1 个内含子变异外,我们还发现了 3 种新的错义变异,但没有拷贝数变异。尽管对照组(n = 800)中没有这些罕见的变异,但我们无法通过分离分析或计算机预测获得致病性的令人信服的证据。因此,我们的数据不支持 VPS35 变异在弗拉芒-比利时人群中路易体障碍遗传病因中的主要作用。