{"title":"C9orf72 gene repeat expansion phenotype profile of motor neurone disease in Portugal","authors":"","doi":"10.1016/j.jns.2024.123208","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p><em>C9orf72</em> 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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>We included 761 patients of whom 61 (8.0 %) were C9RE+. C9RE+ patients had a higher frequency of ALS (95.1 vs 78.4 %, <em>p</em> = 0.002), and lower frequency of progressive muscular atrophy (3.3 vs 16.7 %, <em>p</em> = 0.006). C9RE+ was associated with earlier age of onset (58.1 vs 62.6 years, <em>p</em> = 0.003) and more frequent MND family history (65.5 vs 11.4 %, <em>p</em> < 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 (<em>p</em> = 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, <em>p</em> = 0.008) and ΔF (HR = 1.93, 95 %CI 1.26–2.96, <em>p</em> = 0.002).</p></div><div><h3>Conclusion</h3><p>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.</p></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the Neurological Sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0022510X24003435","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
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.
Methods
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.
Results
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).
Conclusion
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.
期刊介绍:
The Journal of the Neurological Sciences provides a medium for the prompt publication of original articles in neurology and neuroscience from around the world. JNS places special emphasis on articles that: 1) provide guidance to clinicians around the world (Best Practices, Global Neurology); 2) report cutting-edge science related to neurology (Basic and Translational Sciences); 3) educate readers about relevant and practical clinical outcomes in neurology (Outcomes Research); and 4) summarize or editorialize the current state of the literature (Reviews, Commentaries, and Editorials).
JNS accepts most types of manuscripts for consideration including original research papers, short communications, reviews, book reviews, letters to the Editor, opinions and editorials. Topics considered will be from neurology-related fields that are of interest to practicing physicians around the world. Examples include neuromuscular diseases, demyelination, atrophies, dementia, neoplasms, infections, epilepsies, disturbances of consciousness, stroke and cerebral circulation, growth and development, plasticity and intermediary metabolism.