Exploring the phenotype of Italian patients with ALS with intermediateATXN2polyQ repeats
Year: 2022
Type: article
Study design: Observational Study
Abstract: Objective To detect the clinical characteristics of patients with amyotrophic lateral sclerosis (ALS) carrying an intermediateATXN2polyQ number of repeats in a large population-based series of Italian patients with ALS. Methods The study population includes 1330 patients with ALS identified through the Piemonte and Valle d’Aosta Register for ALS, diagnosed between 2007 and 2019 and not carryingC9orf72, SOD1, TARDBPandFUSmutations. Controls were 1274 age, sex and geographically matched Italian subjects, identified through patients’ general practitioners. Results We found 42 cases and 4 controls with≥31 polyQ repeats, corresponding to an estimated OR of 10.4 (95% CI 3.3 to 29.0). Patients with≥31 polyQ repeats (ATXN2+) compared with those without repeat expansion (ATXN2−) had more frequently a spinal onset (p=0.05), a shorter diagnostic delay (p=0.004), a faster rate of ALSFRS-R progression (p=0.004) and King’s progression (p=0.004), and comorbid frontotemporal dementia (7 (28.0%) vs 121 (13.4%), p=0.037). ATXN2+ patients had a 1-year shorter survival (ATXN2+ patients 1.82 years, 95% CI 1.08 to 2.51; ATXN2− 2.84 years, 95% CI 1.67 to 5.58, p=0.0001).ATXN2polyQ intermediate repeats was independently related to a worse outcome in Cox multivariable analysis (p=0.006). Conclusions In our population-based cohort, ATXN2+ patients with ALS have a distinctive phenotype, characterised by a more rapid disease course and a shorter survival. In addition, ATXN2+ patients have a more severe impairment of cognitive functions. These findings have relevant implications on clinical practice, including the possibility of refining the individual prognostic prediction and improving the design of ALS clinical trials, in particular as regards as those targeted explicitly toATXN2.
Authors: Adriano Chio, Cristina Moglia, Antonio Canosa, Umberto Manera, Maurizio Grassano, Rosario Vasta, Francesca Palumbo, Salvatore Gallone, Maura Brunetti, Marco Barberis, Fabiola De Marchi, Clifton Dalgard, Ruth Chia, Gabriele Mora, Barbara Iazzolino, Laura Peotta, Bryan Traynor, Lucia Corrado, Sandra D'Alfonso, Letizia Mazzini, Andrea Calvo
Institutions: Azienda Ospedaliera Citta' della Salute e della Scienza di Torino, University of Turin, Azienda Ospedaliero Universitaria Maggiore della Carita, Uniformed Services University of the Health Sciences, National Institutes of Health, National Institute on Aging, Johns Hopkins University, Università degli Studi del Piemonte Orientale “Amedeo Avogadro”
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: Cytokinetics, European Commission, Ministero della Salute, Ministero dell’Istruzione, dell’Università e della Ricerca, Università degli Studi del Piemonte Orientale, Ministero dell'Università e della Ricerca, National Institutes of Health, National Institute on Aging, H2020 Health, FP7 Health
Awards: G1086909361, G1183686639, G1184370674, G1199795973, BRinging Artificial INTelligencE home for a better cAre of amyotrophic lateral sclerosis and multiple SclERosis, G2170430370, Deconstruct and rebuild phenotypes: a multimodal approach toward personalized medicine in ALS (DECIPHER-ALS), G3207356259, G393177772, G434337789, G4842425482, BRinging Artificial INTelligencE home for a better cAre of amyotrophic lateral sclerosis and multiple SclERosis, G569774987, G5702163051, G581753051, G7697237310, European multidisciplinary ALS network identification to cure motor neuron degeneration, G8878118831, G9000108620
OpenAlex ID: W4293253492