{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:19:37Z","timestamp":1789165177883,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2026,8]]},"abstract":"ABSTRACT<\/jats:title>\n \n Introduction\/Aims<\/jats:title>\n \n Amyotrophic lateral sclerosis (ALS) patients are rarely encountered before age 25\u2009years, often associated with genetic variants.\n SOD1<\/jats:italic>\n gene variants are well\u2010known to account for a subset of adult\u2010onset ALS but have only been described in a handful of early onset patients. Variants affecting residue 125 in\n SOD1<\/jats:italic>\n have been described in adult\u2010onset ALS patients with a rapid progression. Here we report two such patients.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The clinical, genetic, and electrodiagnostic findings of two unrelated adolescents with juvenile onset rapidly progressive\n \n SOD1<\/jats:italic>\n <\/jats:styled-content>\n \u2010\n ALS<\/jats:styled-content>\n are described.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Patient 1 presented at 16 and patient 2 at 15\u2009years\u2010of\u2010age with lower limb onset of weakness, lower motor neuron examination findings, and rapid progression over months to involve all body regions. Both patients underwent extensive laboratory, electrophysiologic, and radiologic testing ruling out any alternate etiologies. For both patients, whole\u2010exome sequencing revealed the pathogenic variant p.\n Asp125Gly<\/jats:styled-content>\n in the\n \n SOD1<\/jats:italic>\n <\/jats:styled-content>\n gene inherited from asymptomatic fathers.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n These two patients expand the phenotypic spectrum of\n \n SOD1<\/jats:italic>\n <\/jats:styled-content>\n \u2010\n ALS<\/jats:styled-content>\n , demonstrating a rapidly progressive juvenile lower limb onset phenotype associated with the p.\n Asp125Gly<\/jats:styled-content>\n variant inherited with incomplete penetrance. Recognition and further characterization of juvenile\n \n SOD1<\/jats:italic>\n <\/jats:styled-content>\n \u2010\n ALS<\/jats:styled-content>\n are important in light of the advances in targeted therapies.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mus.70314","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T06:07:18Z","timestamp":1781071638000},"page":"457-462","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Two Patients With Juvenile\u2010Onset, Rapidly Progressive Amyotrophic Lateral Sclerosis Associated With an\n SOD1<\/scp>\n Variant (\n p.Asp125Gly<\/scp>\n ) With Incomplete Penetrance"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3643-1422","authenticated-orcid":false,"given":"Can","family":"Ozlu","sequence":"first","affiliation":[{"name":"Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2574-2217","authenticated-orcid":false,"given":"Abigail","family":"Schwaede","sequence":"additional","affiliation":[{"name":"Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget","family":"McGowan","sequence":"additional","affiliation":[{"name":"Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Northwestern University Feinberg School of Medicine Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3801-1554","authenticated-orcid":false,"given":"Martha","family":"Finch","sequence":"additional","affiliation":[{"name":"Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa F.","family":"Wolfe","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Northwestern University Feinberg School of Medicine Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senda","family":"Ajroud\u2010Driss","sequence":"additional","affiliation":[{"name":"Department of Neurology Northwestern University Feinberg School of Medicine Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4546-8638","authenticated-orcid":false,"given":"Colin K.","family":"Franz","sequence":"additional","affiliation":[{"name":"Department of Neurology Northwestern University Feinberg School of Medicine Chicago Illinois USA"},{"name":"Department of Pulmonary and Critical Care Medicine Northwestern University Feinberg School of Medicine Chicago Illinois USA"},{"name":"Department of Physical Medicine and Rehabilitation Northwestern University Feinberg School of Medicine Chicago Illinois USA"},{"name":"Department of Physical Therapy and Human Movement Sciences Northwestern University Feinberg School of Medicine Chicago Illinois USA"},{"name":"Shirley Ryan AbilityLab Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Kuntz","sequence":"additional","affiliation":[{"name":"Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine Chicago Illinois USA"},{"name":"Department of Neurology Northwestern University Feinberg School of Medicine Chicago Illinois 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