Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Muscle Nerve. 2010 Aug;42(2):170-6. doi: 10.1002/mus.21665.
Mutations in the fused in sarcoma (FUS) gene have recently been found to cause familial amyotrophic lateral sclerosis (FALS). We screened FUS in a cohort of 200 ALS patients [32 FALS and 168 sporadic ALS (SALS)]. In one FALS proband, we identified a mutation (p.R521C) that was also present in her affected daughter. Their clinical phenotype was remarkably similar and atypical of classic ALS, with symmetric proximal pelvic and pectoral weakness. Distal weakness and upper motor neuron features only developed late. Neuropathological examination demonstrated FUS-immunoreactive neuronal and glial inclusions in the spinal cord and many extramotor regions, but no TDP-43 pathology. We also identified a novel mutation (p.G187S) in one SALS patient. Overall, FUS mutations accounted for 3% of our non-SOD1, non-TARDBP FALS cases and 0.6% of SALS. This study demonstrates that the phenotype with FUS mutations extends beyond classical ALS cases. Our findings suggest there are specific clinicogenetic correlations and provide the first detailed neuropathological description.
融合基因肉瘤（FUS）的突变最近被发现会导致家族性肌萎缩侧索硬化症（FALS）。我们在一个 200 例 ALS 患者队列[32 例 FALS 和 168 例散发性 ALS（SALS）]中筛选了 FUS。在一个 FALS 先证者中，我们发现了一个突变（p.R521C），她患病的女儿也存在这个突变。她们的临床表型非常相似，与典型的 ALS 不同，表现为对称的骨盆和胸部近端无力。远端无力和上运动神经元特征仅在后期出现。神经病理学检查显示脊髓和许多运动外区域存在 FUS 免疫反应性神经元和神经胶质包涵体，但没有 TDP-43 病理学。我们还在一名 SALS 患者中发现了一个新的突变（p.G187S）。总体而言，FUS 突变占我们非 SOD1、非 TARDBP FALS 病例的 3%和 SALS 的 0.6%。这项研究表明，FUS 突变的表型不仅限于经典 ALS 病例。我们的发现表明存在特定的临床遗传相关性，并提供了第一个详细的神经病理学描述。
