{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:46:38Z","timestamp":1785818798057,"version":"3.56.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Amyotrophic lateral sclerosis (ALS) associated with mutations in the superoxide dismutase 1 (\n                      <jats:italic>SOD1<\/jats:italic>\n                      ) gene is recognized for phenotypic variability, yet cerebellar ataxia as a presenting feature has been reported only in isolated cases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We describe four unrelated patients: three men and one woman, aged 35 to 49 years at symptom onset, who carried the\n                      <jats:italic>SOD1<\/jats:italic>\n                      D91A (p.Asp91Ala) mutation. Two patients were heterozygous and two homozygous for the D91A variant. Clinical, neuroimaging, electrophysiological and genetic data were reviewed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All patients presented with progressive gait ataxia as their initial and predominant symptom, with upper and lower motor neuron signs emerging months to years later and ultimately meeting criteria for ALS. Diagnostic latencies from ataxia onset to recognition of ALS ranged from 3 to 9 years. Cerebellar signs included gait and limb ataxia, dysmetria, intention tremor, and oculomotor abnormalities; neuroimaging revealed mild cerebellar atrophy only in one case, and electrophysiological evidence of lower motor neuron involvement was often limited at initial assessment. To our knowledge, this is the largest reported case series of patients homogeneous for a single\n                      <jats:italic>SOD1<\/jats:italic>\n                      mutation and a shared cerebellar ataxia-onset ALS phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The findings expand the clinical spectrum of\n                      <jats:italic>SOD1<\/jats:italic>\n                      -associated ALS and underscore the importance of\n                      <jats:italic>SOD1<\/jats:italic>\n                      genetic testing in patients with progressive adult-onset ataxia of undetermined origin, particularly given the emerging availability of\n                      <jats:italic>SOD1<\/jats:italic>\n                      -targeted therapies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1889931","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:27:19Z","timestamp":1785817639000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cerebellar ataxia-onset ALS with SOD1 D91A mutation: a rare phenotype"],"prefix":"10.3389","volume":"17","author":[{"given":"Denis V.","family":"Shevchuk","sequence":"first","affiliation":[{"name":"Russian Center of Neurology and Neurosciences","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeny P.","family":"Nuzhnyi","sequence":"additional","affiliation":[{"name":"Russian Center of Neurology and Neurosciences","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina Yu.","family":"Fedotova","sequence":"additional","affiliation":[{"name":"Russian Center of Neurology and Neurosciences","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita V.","family":"Ershova","sequence":"additional","affiliation":[{"name":"Russian Center of Neurology and Neurosciences","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan V.","family":"Minaev","sequence":"additional","affiliation":[{"name":"Russian Center of Neurology and Neurosciences","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgy A.","family":"Anikin","sequence":"additional","affiliation":[{"name":"Russian Center of Neurology and Neurosciences","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arina R.","family":"Protsenko","sequence":"additional","affiliation":[{"name":"Russian Center of Neurology and Neurosciences","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia Yu.","family":"Abramycheva","sequence":"additional","affiliation":[{"name":"Russian Center of Neurology and Neurosciences","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria N.","family":"Zakharova","sequence":"additional","affiliation":[{"name":"Russian Center of Neurology and Neurosciences","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey N.","family":"Illarioshkin","sequence":"additional","affiliation":[{"name":"Russian Center of Neurology and Neurosciences","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/S1474-4422(24)00479-4","article-title":"Amyotrophic lateral sclerosis caused by SOD1 variants: from genetic discovery to disease 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