{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:13:07Z","timestamp":1790341987414,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T00:00:00Z","timestamp":1733270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000233","name":"Genome British Columbia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000233","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Spastic tetraplegia and axial hypotonia (STAHP) associated with biallelic\n                    <jats:italic>SOD1<\/jats:italic>\n                    deficiency is a recently described neurological disorder affecting children. Five studies have described a total of nine cases thus far, all characterized by the onset of progressive spastic tetraplegia beginning before 2\u2009years of age. All but two of these cases are associated with homozygosity for the same genetic variant (NM_000454.4:c.335dupG; NP_000445.1:p.Cys112Trpfs*11) that leads to a non\u2010functional enzyme product. More recently, a homozygous 3\u2010base pair in\u2010frame deletion (NM_000454.5: c.357_357+2delGGT) and a truncating frameshift variant (NM_000454.5: c.52_56del5ins154) in\n                    <jats:italic>SOD1<\/jats:italic>\n                    have been described in similarly affected patients lacking SOD1 activity. Here we expand on the neurological and extra\u2010neuronal phenotypes of STAHP in a patient with a novel homozygous\n                    <jats:italic>SOD1<\/jats:italic>\n                    variant predicted to result in disrupted calcium\u2010 and zinc\u2010binding activity of the encoded enzyme. We describe a 19\u2010year\u2010old male born to consanguineous parents who is homozygous for an NM_000454.4:c.369_371del\n                    <jats:italic>SOD1<\/jats:italic>\n                    variant. The patient had progressive neuromuscular degeneration with onset before 1\u2009year of age, consistent with a diagnosis of STAHP. Brain MRI at 7\u2009years of age showed cerebellar atrophy, as has previously been described in this condition, as well as small optic nerves and a hypoplastic optic chiasm, which have not been reported previously. Our patient also exhibited clinical features of immune dysregulation with treatment\u2010refractory inflammatory bowel disease, asthma, recurrent infections, and dermatitis. Overall, the early\u2010onset progressive neurological disorder in our patient, found in association with homozygosity for an\n                    <jats:italic>SOD1<\/jats:italic>\n                    variant that is predicted to result in impaired function of the transcribed protein, is consistent with a diagnosis of STAHP. Our patient also demonstrates optic atrophy and disrupted immune homeostasis, which have not been previously described as part of this condition. Taken together with previous case studies in children carrying loss\u2010of\u2010function variants of\n                    <jats:italic>SOD1<\/jats:italic>\n                    , this case highlights a possible role for antioxidant therapy in slowing disease progression in patients lacking SOD1 activity. These cases also draw attention to the need for careful consideration of possible harmful neuronal and extra\u2010neuronal complications of proposed\n                    <jats:italic>SOD1<\/jats:italic>\n                    knockdown therapies against ALS.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.63949","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T05:31:32Z","timestamp":1733290292000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Immune Dysregulation in a Child With\n                    <i>SOD1<\/i>\n                    \u2010Related Neurological Disease"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1598-0104","authenticated-orcid":false,"given":"Rozlyn Claire Thomas","family":"Boutin","sequence":"first","affiliation":[{"name":"Provincial Medical Genetics Program British Columbia Women's Hospital  Vancouver British 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Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0636-123X","authenticated-orcid":false,"given":"Anna","family":"Lehman","sequence":"additional","affiliation":[{"name":"Adult Metabolic Diseases Clinic Vancouver General Hospital  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8132-9136","authenticated-orcid":false,"given":"Ramona","family":"Salvarinova","sequence":"additional","affiliation":[{"name":"Division of Biochemical Genetics, Department of Pediatrics British Columbia Children's Hospital  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7482-9570","authenticated-orcid":false,"given":"Jan M","family":"Friedman","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine The University of British Columbia  Vancouver British 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