Footnotes

• Contributors All authors made substantial contributions to study conception and design and/or acquisition of data and/or analysis and interpretation of data. All authors gave final approval of the version to be submitted and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Conception and design of the study: FV, VS. Sample collection, phenotyping and data management: FV, GZ, SP, NT, CM, AD, SM, LM, CC, VG, CT, VS. Study management and coordination: FV, VS. Statistical methods and analysis: DS, AZ, FV. Laboratory analyses: GZ, CB, MOB, SP. Interpretation of results: FV, GZ, CB, MOB, DS, SP, NT, CM, CC, PLM, AZ, AR, VS. Manuscript writing (first draft): FV. Critical revision of the manuscript: FV, GZ, CB, MOB, DS, SP, NT, CM, AD, SM, LM, CC, VG, CT, PLM, AZ, AR, VS.

• Funding The work was financially supported by the Italian Ministry of Health (grant RF-2013–02355764, C9GenALSPhen).

• Competing interests VS is in the Editorial Board of Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, European Neurology, American Journal of Neurodegenerative Disease, and Frontiers in Neurology, and received compensation for consulting services and/or speaking activities from AveXis, Cytokinetics, Italfarmaco and Zambon.

• Patient consent for publication Not required.

• Ethics approval The study was approved by the Ethics Committee of Istituto Auxologico Italiano, IRCCS (ID: 2020_05_19_07). Patients provided written informed consent for the study.

• Provenance and peer review Not commissioned; externally peer reviewed.