Schottlaender Lucia V, Polke James M, Ling Helen, MacDoanld Nicola D, Tucci Arianna, Nanji Tina, Pittman Alan, de Silva Rohan, Holton Janice L, Revesz Tamas, Sweeney Mary G, Singleton Andy B, Lees Andrew J, Bhatia Kailash P, Houlden Henry
Department of Molecular Neuroscience, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK.
Department of Molecular Neuroscience, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK; Neurogenetics Laboratory, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK.
Neurobiol Aging. 2015 Feb;36(2):1221.e1-6. doi: 10.1016/j.neurobiolaging.2014.08.024. Epub 2014 Aug 27.
A GGGGCC repeat expansion in the C9orf72 gene was recently identified as a major cause of familial and sporadic amyotrophic lateral sclerosis and frontotemporal dementia. There is suggestion that these expansions may be a rare cause of parkinsonian disorders such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal degeneration (CBD). Screening the C9orf72 gene in 37 patients with features of corticobasal syndrome (CBS) detected an expansion in 3 patients, confirmed by Southern blotting. In a series of 22 patients with clinically diagnosed PSP, we found 1 patient with an intermediate repeat length. We also screened for the C9orf72 expansion in a large series of neuropathologically confirmed samples with MSA (n = 96), PSP (n = 177), and CBD (n = 18). Patients were found with no more than 22 GGGGCC repeats. Although these results still need to be confirmed in a larger cohort of CBS and/or CBD patients, these data suggest that in the presence of a family history and/or motor neuron disease features, patients with CBS or clinical PSP should be screened for the C9orf72 repeat expansion. In addition, we confirm that the C9orf72 expansions are not associated with pathologically confirmed MSA, PSP, or CBD in a large series of cases.
最近发现，C9orf72基因中的GGGGCC重复序列扩增是家族性和散发性肌萎缩侧索硬化症以及额颞叶痴呆的主要病因。有迹象表明，这些扩增可能是帕金森氏症如进行性核上性麻痹（PSP）、多系统萎缩（MSA）和皮质基底节变性（CBD）的罕见病因。对37例具有皮质基底节综合征（CBS）特征的患者进行C9orf72基因筛查，经Southern印迹法确认，3例患者存在扩增。在一系列22例临床诊断为PSP的患者中，我们发现1例患者的重复长度处于中间值。我们还对大量经神经病理学确诊的MSA（n = 96）、PSP（n = 177）和CBD（n = 18）样本进行了C9orf72扩增筛查。发现患者的GGGGCC重复序列不超过22个。尽管这些结果仍需在更大规模的CBS和/或CBD患者队列中得到证实，但这些数据表明，在存在家族病史和/或运动神经元疾病特征的情况下，CBS或临床PSP患者应进行C9orf72重复序列扩增筛查。此外，我们证实，在大量病例中，C9orf72扩增与经病理证实的MSA、PSP或CBD无关。
