{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T19:52:53Z","timestamp":1781639573477,"version":"3.54.5"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004913","name":"Universit\u00e0 degli Studi di Palermo","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004913","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurol Sci"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Approximately 10% of ALS (amyotrophic lateral sclerosis) cases show a family history, and the remaining 90% are sporadic. In 2018, through genome sequencing using two independent approaches, KIF5A was described as a novel ALS-associated gene. To describe clinical and genetic characteristics of a series of patients with motor neuron disease (MND), diagnosed at University Hospital of Palermo, carrying KIF5A variants. During 2019\u20132023, two hundred twenty-four patients with MND and healthy subjects with familial history of MND, underwent next-generation sequencing (NGS) for molecular analysis, including genetic testing for C9orf72 hexanucleotide-repeat expansion. The most mutated ALS genes, including KIF5A, were included in a NGS panel. Of the entire tested population, eight patients (including a brother and a sister) were found to carry KIF5A variants. Four patients had familial ALS, the other four were sporadic. Six patients were females (75%). Mean age at ALS onset was 59 years (33\u201375). Patients were evaluated according to the ALSFRS-revisited during follow-up visits. According to disease progression rate, five patients were defined as \u2206FS\u2009\u2264\u20090.5 (slow-progressors), the remaining three patients showed a \u2206FS\u2009&gt;\u20091 (fast-progressors). Of the seven KIF5A variants, three are not already described in literature (respectively c.170\u00a0C\u2009&gt;\u2009T, p.Thr57Met; c.2920T\u2009&gt;\u2009G, p.Ser974Ala and c.2732\u00a0A\u2009&gt;\u2009C, p.Lys911Thr). Two patients showed the association of variations in KIF5A with variations or mutations in other ALS genes, one of them carried a pathogenic variant of FUS (P525L). This study demonstrates phenotypic variability related to mutations in different regions of the same gene resulting in a susceptibility for the disease spectrum with different characteristics.<\/jats:p>","DOI":"10.1007\/s10072-026-08885-w","type":"journal-article","created":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T03:28:38Z","timestamp":1772249318000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["KIF5A and ALS: a clinical and genetic description of a case series and review of literature"],"prefix":"10.1007","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1938-9677","authenticated-orcid":false,"given":"Anna","family":"D\u2019Amico","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3442-984X","authenticated-orcid":false,"given":"Roberta","family":"Cucunato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9632-1994","authenticated-orcid":false,"given":"Giuseppe","family":"Schir\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3756-4323","authenticated-orcid":false,"given":"Giuseppe","family":"Salemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2516-1567","authenticated-orcid":false,"given":"Paolo","family":"Ragonese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"La Bella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7424-9533","authenticated-orcid":false,"given":"Paolo","family":"Aridon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2178-6749","authenticated-orcid":false,"given":"Marco","family":"D\u2019Amelio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"8885_CR1","doi-asserted-by":"crossref","unstructured":"Hardiman O, Al-Chalabi A, Chio A, Corr EM, Logroscino G, Robberecht W et al (2017) Amyotrophic lateral sclerosis. Nature Reviews Disease Primers [Internet]. ;3(1). Available from: https:\/\/www.nature.com\/articles\/nrdp201771","DOI":"10.1038\/nrdp.2017.85"},{"issue":"4","key":"8885_CR2","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1016\/j.neuron.2010.09.039","volume":"68","author":"N Hirokawa","year":"2010","unstructured":"Hirokawa N, Niwa S, Tanaka Y (2010) Molecular motors in neurons: transport mechanisms and roles in brain function, development, and disease. Neuron 68(4):610\u2013638","journal-title":"Neuron"},{"key":"8885_CR3","doi-asserted-by":"crossref","unstructured":"Kardon JR, Vale RD Regulators of the cytoplasmic dynein motor. Nature Reviews Molecular Cell Biology [Internet]. 2009 Dec 1 [cited 2022 Jan 28];10(12):854\u201365. 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Nature 377(6548):448\u201350","journal-title":"Nature"},{"issue":"10","key":"8885_CR6","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1038\/nrm2774","volume":"10","author":"N Hirokawa","year":"2009","unstructured":"Hirokawa N, Noda Y, Tanaka Y, Niwa S (2009) Kinesin superfamily motor proteins and intracellular transport. Nat Rev Mol Cell Biol 10(10):682\u2013696","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"3","key":"8885_CR7","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1093\/brain\/awx370","volume":"141","author":"D Brenner","year":"2018","unstructured":"Brenner D, Yilmaz R, M\u00fcller K, Grehl T, Petri S, Meyer T et al (2018) Hot-spot KIF5A mutations cause Familial ALS. 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Available from: https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0002929707604121?via%3Dihub","journal-title":"The American Journal of Human Genetics"},{"issue":"6","key":"8885_CR10","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1111\/gtc.12936","volume":"27","author":"J Nakano","year":"2022","unstructured":"Nakano J, Chiba K, Niwa S (2022) An ALS-associated KIF5A mutant forms oligomers and aggregates and induces neuronal toxicity. Genes to Cells [Internet]. ;27(6):421\u201335. Available from: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9322661\/","journal-title":"Genes to Cells"},{"key":"8885_CR11","doi-asserted-by":"crossref","unstructured":"Pant DC, Parameswaran J, Rao L, Loss I, Chilukuri G, Parlato R et al (2022) ALS -linked KIF5A \u2206Exon27 mutant causes neuronal toxicity through gain\u2010of\u2010function. 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