{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:27:36Z","timestamp":1765844856611,"version":"3.48.0"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["25wm0625126s0301"],"award-info":[{"award-number":["25wm0625126s0301"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Herein, we report an autopsy case of sporadic amyotrophic lateral sclerosis (ALS) with a p. L127S (L126S)\n                    <jats:italic>SOD1<\/jats:italic>\n                    variant,\n                    <jats:italic>SMN2<\/jats:italic>\n                    deletion and one hybrid\n                    <jats:italic>SMN<\/jats:italic>\n                    . A 43\u2010year\u2010old Japanese man noticed muscle weakness in his left lower extremity. At the age of 51, his muscle strength was moderately diminished in the upper extremities and severely in the lower extremities with hyporeflexia. At the age of 55, he started noninvasive intermittent ventilation (NIV) during nighttime. At the age of 57, he developed dysphagia and died of pneumonia. The total clinical course was 14\u2009years and 8\u2009months (13\u2009years 9\u2009months until NIV). Pathologically we found severe loss of lower motor neurons, moderate neuronal loss in Clarke's nuclei and mild grumose degeneration of the dentate nucleus. The primary motor cortex was well preserved and the pyramidal tracts showed vague myelin pallor in the lumbar cord. There were a few conglomerate hyaline inclusions (CHIs) that were negative for Bodian staining. Immunohistochemically, CHIs were positive for phosphorylated neurofilament (pNF) and were stained with Uq and SOD1 to varying degrees. Some CHIs contained granular\u2010like components positive for p62. A post\u2010mortem genetic test revealed that the patient had 2 copies of\n                    <jats:italic>SMN1<\/jats:italic>\n                    , 0 copies of\n                    <jats:italic>SMN2<\/jats:italic>\n                    , and one hybrid gene with exon 1 to 7 of\n                    <jats:italic>SMN2<\/jats:italic>\n                    and\n                    <jats:italic>SMN1<\/jats:italic>\n                    exon 8. Additional gene research elucidated a heterozygous\n                    <jats:italic>SOD1<\/jats:italic>\n                    p. Leu127Ser (L126S) mutation. Compared to previous reports of ALS with the same mutation, the distribution of degenerative lesions was similar. It has been suggested that\n                    <jats:italic>SMN2<\/jats:italic>\n                    deletion may not be directly implicated in lower motor neuron pathology, but further research is needed to confirm this. Further accumulation of cases is necessary to determine the effect of\n                    <jats:italic>SMN2<\/jats:italic>\n                    on\n                    <jats:italic>SOD1<\/jats:italic>\n                    \u2010ALS.\n                  <\/jats:p>","DOI":"10.1111\/neup.70032","type":"journal-article","created":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T07:49:11Z","timestamp":1763192951000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Autopsy Case of\n                    <scp>ALS<\/scp>\n                    Which Clinically Presented Sporadic Adult\u2010Onset Lower Motor Neuron Disease and Genetically Had p.\n                    <scp>Leu127Ser<\/scp>\n                    (\n                    <scp>L126S<\/scp>\n                    ) Variant in\n                    <scp>\n                      <i>SOD1<\/i>\n                    <\/scp>\n                    and\n                    <scp>\n                      <i>SMN2<\/i>\n                    <\/scp>\n                    Deletion"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0216-9787","authenticated-orcid":false,"given":"Kimiko","family":"Inoue","sequence":"first","affiliation":[{"name":"Department of Neurology and Pathology National Hospital Organization Osaka Toneyama Medical Center  Toyonaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harutoshi","family":"Fujimura","sequence":"additional","affiliation":[{"name":"Department of Neurology and Pathology National Hospital Organization Osaka Toneyama Medical Center  Toyonaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kayo","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Neurology and Pathology National Hospital Organization Osaka Toneyama Medical Center  Toyonaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisahide","family":"Nishio","sequence":"additional","affiliation":[{"name":"Department\u00a0of\u00a0Occupational Therapy, Faculty of Rehabilitation Kobe Gakuin University  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1190-0499","authenticated-orcid":false,"given":"Hiroya","family":"Naruse","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate\u00a0School of Medicine The\u00a0University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuishin","family":"Izumi","sequence":"additional","affiliation":[{"name":"Department of Neurology Tokushima University Graduate School of Biomedical Sciences  Tokushima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,14]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2015.11.030"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000200196"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010002\u20100811\u20104"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181c5e713"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2020.09.005"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920\u2010024\u201002026\u2010y"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000200175"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26009"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0022\u2010510x(01)00558\u20105"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.58.5.736"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/neup.12620"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/neup.70028"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010003\u20100743\u20109"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440\u20101789.2008.00910.x"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/neup.12784"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410430513"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004150200007"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000233830.85206.1e"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.255"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.3349\/ymj.2012.53.1.53"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcaa075"}],"container-title":["Neuropathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/neup.70032","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:26:20Z","timestamp":1765844780000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/neup.70032"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,14]]},"references-count":21,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1111\/neup.70032"],"URL":"https:\/\/doi.org\/10.1111\/neup.70032","archive":["Portico"],"relation":{},"ISSN":["0919-6544","1440-1789"],"issn-type":[{"type":"print","value":"0919-6544"},{"type":"electronic","value":"1440-1789"}],"subject":[],"published":{"date-parts":[[2025,11,14]]},"assertion":[{"value":"2025-09-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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