Department of Neurosciences and Mental Health, Unidade Local de Saúde de Santa Maria, Lisbon, Portugal; Faculdade de Medicina-Instituto de Medicina Molecular, Centro de Estudos Egas Moniz, Universidade de Lisboa, Lisboa, Portugal.
Faculdade de Medicina-Instituto de Medicina Molecular, Centro de Estudos Egas Moniz, Universidade de Lisboa, Lisboa, Portugal.
J Neurol Sci. 2024 Oct 15;465:123208. doi: 10.1016/j.jns.2024.123208. Epub 2024 Aug 30.
C9orf72 gene repeat expansion (C9RE) is the most frequent gene variant associated with amyotrophic lateral sclerosis (ALS). We aimed to study the phenotype of motor neurone disease (MND) patients with C9RE in a Portuguese cohort.
Demographical and clinical data of MND patients with (C9RE+) and without C9RE were compared. ALS al Rating Scale-Revised (ALSFRS-R) and Edinburgh Cognitive and Behavioural ALS Screen (ECAS) were used to evaluate functional and cognitive performance, respectively. Survival analysis was performed using Kaplan Meier log-rank test and Cox proportional hazards model.
We included 761 patients of whom 61 (8.0 %) were C9RE+. C9RE+ patients had a higher frequency of ALS (95.1 vs 78.4 %, p = 0.002), and lower frequency of progressive muscular atrophy (3.3 vs 16.7 %, p = 0.006). C9RE+ was associated with earlier age of onset (58.1 vs 62.6 years, p = 0.003) and more frequent MND family history (65.5 vs 11.4 %, p < 0.001). Gender, ethnicity, onset site, diagnostic delay, disease progression rate until diagnosis (ΔF), ALSFRS-R and time until non-invasive ventilation did not differ between groups. Cognitive/behavioural symptoms and ECAS did not differ between groups, except a worse visuospatial score in C9RE+ group (p = 0.035). Death rate was 1.8 and 1.6 times higher in C9RE+ patients with MND and ALS, respectively. Significant survival prognostic factors in C9RE+ group were diagnosis delay (HR = 0.96, 95 %CI 0.92-0.99, p = 0.008) and ΔF (HR = 1.93, 95 %CI 1.26-2.96, p = 0.002).
Our study corroborates most previous cohorts' findings, but harbours some singularities regarding onset site, phenotype, and cognitive profile, that contribute to a better understanding of C9RE epidemiology.
C9orf72 基因重复扩展（C9RE）是与肌萎缩侧索硬化症（ALS）最相关的最常见基因变异。我们旨在研究葡萄牙队列中 C9RE 与运动神经元病（MND）患者的表型。
比较了 C9RE（C9RE+）和无 C9RE 的 MND 患者的人口统计学和临床数据。使用 ALS 功能评定量表修订版（ALSFRS-R）和爱丁堡认知和行为 ALS 筛查（ECAS）分别评估功能和认知表现。使用 Kaplan-Meier 对数秩检验和 Cox 比例风险模型进行生存分析。
我们纳入了 761 名患者，其中 61 名（8.0%）为 C9RE+。C9RE+患者的 ALS 发生率更高（95.1%比 78.4%，p=0.002），进展性肌肉萎缩的发生率更低（3.3%比 16.7%，p=0.006）。C9RE+与发病年龄较早相关（58.1 岁比 62.6 岁，p=0.003），且更常伴有 MND 家族史（65.5%比 11.4%，p<0.001）。性别、种族、发病部位、诊断延迟、诊断至非侵入性通气的疾病进展率（ΔF）、ALSFRS-R 和非侵入性通气时间在两组间无差异。认知/行为症状和 ECAS 在两组间无差异，除 C9RE+组的视觉空间评分更差（p=0.035）外。C9RE+的 MND 和 ALS 患者的死亡率分别高出 1.8 和 1.6 倍。C9RE+患者的显著生存预后因素包括诊断延迟（HR=0.96，95%CI 0.92-0.99，p=0.008）和 ΔF（HR=1.93，95%CI 1.26-2.96，p=0.002）。
本研究证实了大多数先前队列的研究结果，但在发病部位、表型和认知特征方面存在一些特殊性，有助于更好地了解 C9RE 的流行病学。
