Experimental Neuropathology Unit, Institute of Experimental Neurology (INSPE), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Neurology Unit, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy.
J Neurol. 2024 Mar;271(3):1342-1354. doi: 10.1007/s00415-023-12074-6. Epub 2023 Nov 6.
Amyotrophic lateral sclerosis associated with mutations in SOD1 (SOD1-ALS) might be susceptible to specific treatment. The aim of the study is to outline the clinical features of SOD1-ALS patients by comparing them to patients without ALS major gene variants and patients with variants in other major ALS genes. Defining SOD1-ALS phenotype may assist clinicians in identifying patients who should be prioritized for genetic testing.
We performed an extensive literature research including original studies which reported the clinical features of SOD1-ALS and at least one of the following patient groups: C9ORF72 hexanucleotide repeat expansion (C9-ALS), TARDBP (TARDBP-ALS), FUS (FUS-ALS) or patients without a positive test for a major-ALS gene (N-ALS). A random effects meta-analytic model was applied to clinical data extracted encompassing sex, site and age of onset. To reconstruct individual patient survival data, the published Kaplan-Meier curves were digitized. Data were measured as odds ratio (OR) or standardized mean difference (SMD) as appropriate. Median survival was compared between groups.
Twenty studies met the inclusion criteria. We identified 721 SOD1-ALS, 470 C9-ALS, 183 TARDBP-ALS, 113 FUS-ALS and 2824 N-ALS. SOD1-ALS showed a higher rate of spinal onset compared with N-ALS and C9-ALS (OR = 4.85, 95% CI = 3.04-7.76; OR = 10.47, 95% CI = 4.32-27.87) and an earlier onset compared with N-ALS (SMD = - 0.45, 95% CI = - 0.72 to - 0.18). SOD1-ALS had a similar survival compared with N-ALS (p = 0.14), a longer survival compared with C9-ALS (p < 0.01) and FUS-ALS (p = 0.019) and a shorter survival compared with TARDBP-ALS (p < 0.01).
This study indicates the presence of a specific SOD1-ALS phenotype. Insights in SOD1-ALS clinical features are important in genetic counseling, disease prognosis and support patients' stratification in clinical trials.
携带有 SOD1 基因突变的肌萎缩侧索硬化症（SOD1-ALS）可能对特定治疗方法敏感。本研究旨在通过比较 SOD1-ALS 患者与无 ALS 主要基因变异患者和其他主要 ALS 基因变异患者，来描述 SOD1-ALS 患者的临床特征。明确 SOD1-ALS 表型可能有助于临床医生识别应优先进行基因检测的患者。
我们进行了广泛的文献研究，包括报告 SOD1-ALS 临床特征的原始研究，以及至少一个以下患者群体的研究：C9ORF72 六核苷酸重复扩展（C9-ALS）、TARDBP（TARDBP-ALS）、FUS（FUS-ALS）或无主要 ALS 基因阳性检测结果的患者（N-ALS）。应用随机效应荟萃分析模型提取包含性别、发病部位和发病年龄的临床数据。为了重建个体患者的生存数据，对已发表的 Kaplan-Meier 曲线进行了数字化。数据以比值比（OR）或标准化均数差（SMD）表示。比较组间中位生存期。
20 项研究符合纳入标准。我们共确定了 721 例 SOD1-ALS、470 例 C9-ALS、183 例 TARDBP-ALS、113 例 FUS-ALS 和 2824 例 N-ALS。与 N-ALS 和 C9-ALS 相比，SOD1-ALS 更易出现脊髓发病（OR=4.85，95%CI=3.04-7.76；OR=10.47，95%CI=4.32-27.87）且发病年龄更早（SMD=-0.45，95%CI=-0.72 至-0.18）。与 N-ALS 相比，SOD1-ALS 的生存率相似（p=0.14），与 C9-ALS（p<0.01）和 FUS-ALS（p=0.019）相比生存率更长，与 TARDBP-ALS 相比生存率更短（p<0.01）。
本研究表明存在特定的 SOD1-ALS 表型。深入了解 SOD1-ALS 的临床特征对于遗传咨询、疾病预后和支持患者在临床试验中的分层具有重要意义。
