Farrer Matthew J, Hulihan Mary M, Kachergus Jennifer M, Dächsel Justus C, Stoessl A Jon, Grantier Linda L, Calne Susan, Calne Donald B, Lechevalier Bernard, Chapon Francoise, Tsuboi Yoshio, Yamada Tatsuo, Gutmann Ludwig, Elibol Bülent, Bhatia Kailash P, Wider Christian, Vilariño-Güell Carles, Ross Owen A, Brown Laura A, Castanedes-Casey Monica, Dickson Dennis W, Wszolek Zbigniew K
Division of Neurogenetics, Department of Neuroscience, Mayo Clinic Florida, Jacksonville, Florida 32224, USA.
Nat Genet. 2009 Feb;41(2):163-5. doi: 10.1038/ng.293. Epub 2009 Jan 11.
Perry syndrome consists of early-onset parkinsonism, depression, severe weight loss and hypoventilation, with brain pathology characterized by TDP-43 immunostaining. We carried out genome-wide linkage analysis and identified five disease-segregating mutations affecting the CAP-Gly domain of dynactin (encoded by DCTN1) in eight families with Perry syndrome; these mutations diminish microtubule binding and lead to intracytoplasmic inclusions. Our findings show that DCTN1 mutations, previously associated with motor neuron disease, can underlie the selective vulnerability of other neuronal populations in distinct neurodegenerative disorders.
佩里综合征包括早发性帕金森症、抑郁症、严重体重减轻和通气不足，其脑部病理学特征为TDP-43免疫染色。我们进行了全基因组连锁分析，并在8个佩里综合征家族中鉴定出5个影响动力蛋白（由DCTN1编码）的CAP-Gly结构域的疾病分离突变；这些突变减少了微管结合并导致胞质内包涵体形成。我们的研究结果表明，先前与运动神经元疾病相关的DCTN1突变，可能是不同神经退行性疾病中其他神经元群体选择性易损性的基础。
