Northcott Neuroscience Laboratory, ANZAC Research Institute, Sydney, NSW, Australia.
Neurobiol Aging. 2013 Sep;34(9):2235.e7-10. doi: 10.1016/j.neurobiolaging.2013.04.003. Epub 2013 Apr 28.
Mutations in PFN1, a gene encoding the actin monomer-binding protein profilin 1, were recently reported in 1% to 2% of familial amyotrophic lateral sclerosis (ALS) patients. In vitro functional studies suggested that PFN1 mutations lead to ubiquitin-positive inclusions and impairment of cytoskeletal pathways. In the present study, mutation analysis of PFN1 was performed in an Australian cohort of 110 ALS families and 715 sporadic ALS patients. No PFN1 mutations were identified in familial ALS patients. Two rare non-synonymous variants (E117D and E117G) were found in sporadic ALS patients at similar incidences to that reported in public SNP databases. Immunostaining of PFN1 in sporadic ALS and familial ALS patients, including those with mutations in SOD1, FUS, UBQLN2 and C9ORF72, found no PFN1-positive inclusions in spinal motor neurons. Our data suggest that PFN1 mutations and pathology are not common in an Australian ALS cohort of predominantly European ancestry.
PFN1 基因突变，该基因编码肌动蛋白单体结合蛋白原肌球蛋白 1，最近在 1%至 2%的家族性肌萎缩侧索硬化症（ALS）患者中报道。体外功能研究表明，PFN1 突变导致泛素阳性包涵体和细胞骨架途径受损。在本研究中，对 110 个澳大利亚 ALS 家族和 715 例散发性 ALS 患者的 PFN1 进行了突变分析。在家族性 ALS 患者中未发现 PFN1 突变。在散发性 ALS 患者中发现了两种罕见的非同义变异（E117D 和 E117G），其发生率与公共 SNP 数据库报道的相似。对包括 SOD1、FUS、UBQLN2 和 C9ORF72 突变的散发性 ALS 和家族性 ALS 患者的 PFN1 免疫染色未发现脊髓运动神经元中存在 PFN1 阳性包涵体。我们的数据表明，PFN1 突变和病理学在主要为欧洲血统的澳大利亚 ALS 队列中并不常见。
