Objectives This study compares the clinical characteristics of patients with amyotrophic lateral sclerosis (ALS) within three clinic-based populations from Cuba, Uruguay and Ireland and determines the impact of known ALS-associated genetic variants on phenotypic manifestations within the Cuban population.
Methods Demographic and clinical information was collected on 115 Cuban, 220 Uruguayan and 1038 Irish patients with ALS attending national specialist clinics through 1996–2017. All Cuban patients and 676 Irish patients underwent next-generation DNA sequencing and were screened for the pathogenic C9orf72 repeat expansion.
Results The mean age of onset was younger in the Cuban (53.0 years, 95% CI 50.4 to 55.6) and Uruguayan (58.2 years, 95% CI 56.5 to 60.0) populations compared with the Irish population (61.6 years, 95% CI 60.9 to 62.4). No differences in survival between populations were observed. 1.7 % (95% CI 0.6 to 4.1) of Cubans with ALS carried the C9orf72 repeat expansion compared with 9.9% (95% CI 7.8 to 12.0) of Irish patients with ALS (p=0.004). Other known variants identified in the Cuban population included ANG (one patient), CHCHD10 (one patient) and DCTN1 (three patients).
Conclusions and relevance This study is the first to describe the clinical characteristics of ALS in Cuban and Uruguayan populations and report differences between the Cuban and Irish genetic signature in terms of known ALS-associated genetic variants. These novel clinical and genetic data add to our understanding of ALS across different and understudied populations.
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MR and TZV contributed equally.
Contributors MR: study concept and design, analysis and interpretation of data, manuscript composition. TZV: study concept and design, acquisition of data, analysis and interpretation of data, revision of manuscript for intellectual content. RLM, MAD: acquisition of data, analysis and interpretation of data. JR, MH: study concept and design, acquisition of data, analysis and interpretation of data, revision of manuscript for intellectual content. JG, GEL-F, JH, MCV: study concept and design, acquisition of data. MPR: study concept and design, analysis and interpretation of data. AP: study concept and design, acquisition of data, analysis and interpretation of data. MM, CNK: study concept and design. GL, OH: study concept and design, analysis and interpretation of data, revision of manuscript for intellectual content. MR: statistical analysis.
Funding This project is the work of the Latin-American Epidemiology Network of ALS (LAENALS), supported through funding provided by the Centers for Disease Control and Prevention (Award TS000242). MR and MAD receive support from Science Foundation Ireland. TZV, JG, GEL-F and MPR receive support from the Ministry of Public Health Cuba. RLM receives support from the Motor Neurone Disease Association (MNDA). OH receives support from the Health Research Board including Joint Programme in Neurodegeneration, Research Motor Neurone and Science Foundation Ireland (FutureNeuro Centre).
Competing interests OH has received speaker honoraria/travel funding from Janssen Cilag, Biogen Idec, Sanofi Aventis, Novartis and Merck-Serono; has been a member of advisory panels for Biogen Idec, Allergan, Ono Pharmaceutical, Novartis, Cytokinetics, Treeway, Wave, NINDS CDE Team for ALS/MND and Sanofi Aventis; serves as Editor-in-Chief of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia; serves on the editorial board of the Journal of Neurology, Neurosurgery, and Psychiatry; coholds patents for Treatment of Central Nervous System Injury Inventors (RCSI); consults for Biogen Idec and Cytokinetics; and has received research support from Science Foundation Ireland.
Patient consent for publication Not required.
Ethics approval Informed written consent was obtained from all participants, and the study was approved by the research and ethics committees of all participating institutes.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Data can be obtained on request through the LAENALS management team (firstname.lastname@example.org), which has a protocol for approving data requests. Data cannot be made publicly available because of restrictions based on informed consent of the participants.
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