Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
Neurobiol Aging. 2012 Apr;33(4):837.e7-13. doi: 10.1016/j.neurobiolaging.2011.10.006. Epub 2011 Nov 10.
Mutations in the valosin-containing protein (VCP) gene were recently reported to be the cause of 1%-2% of familial amyotrophic lateral sclerosis (ALS) cases. VCP mutations are known to cause inclusion body myopathy (IBM) with Paget's disease (PDB) and frontotemporal dementia (FTD). The presence of VCP mutations in patients with sporadic ALS, sporadic ALS-FTD, and progressive muscular atrophy (PMA), a known clinical mimic of inclusion body myopathy, is not known. To determine the identity and frequency of VCP mutations we screened a cohort of 93 familial ALS, 754 sporadic ALS, 58 sporadic ALS-FTD, and 264 progressive muscular atrophy patients for mutations in the VCP gene. Two nonsynonymous mutations were detected; 1 known mutation (p.R159H) in a patient with familial ALS with several family members suffering from FTD, and 1 mutation (p.I114V) in a patient with sporadic ALS. Conservation analysis and protein prediction software indicate the p.I114V mutation to be a rare benign polymorphism. VCP mutations are a rare cause of familial ALS. The role of VCP mutations in sporadic ALS, if present, appears limited.
最近有报道称，包含缬氨酸蛋白（VCP）基因突变是 1%-2%家族性肌萎缩侧索硬化症（ALS）病例的病因。VCP 突变已知会导致包涵体肌病（IBM）伴 Pagets 病（PDB）和额颞叶痴呆（FTD）。VCP 突变在散发性 ALS、散发性 ALS-FTD 和进行性肌萎缩症（PMA）患者中的存在情况尚不清楚，PMA 是 IBM 的已知临床模拟疾病。为了确定 VCP 基因突变的存在和频率，我们对 93 名家族性 ALS、754 名散发性 ALS、58 名散发性 ALS-FTD 和 264 名进行性肌萎缩症患者的 VCP 基因进行了筛查。检测到两个非同义突变；一个是家族性 ALS 患者的已知突变（p.R159H），该患者有多个家族成员患有 FTD，另一个是散发性 ALS 患者的突变（p.I114V）。保守性分析和蛋白质预测软件表明 p.I114V 突变是一种罕见的良性多态性。VCP 突变是家族性 ALS 的罕见病因。如果存在 VCP 突变，在散发性 ALS 中的作用似乎有限。
