{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:04:26Z","timestamp":1787738666466,"version":"build-2784847793"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T00:00:00Z","timestamp":1694563200000},"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:p>Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons, with occasional involvement of the extrapyramidal system. Mutations in the sigma non-opioid intracellular receptor 1 (<jats:italic>SIGMAR1<\/jats:italic>) gene have been identified as one of the causes of ALS. Here, we present a case of a 49-year-old man diagnosed with ALS\u2013Parkinson\u2019s disease (PD) complex. The patient exhibited bradykinesia and tremor, and whole-exome sequencing revealed homozygous mutations in the <jats:italic>SIGMAR1<\/jats:italic> gene (c.446-2A\u2009&amp;gt;\u2009T). In addition, we conducted an investigation into the clinical and molecular phenotype of previously reported variants of <jats:italic>SIGMAR1<\/jats:italic> associated with ALS. This case report aims to raise awareness among physicians regarding atypical phenotypes of amyotrophic lateral sclerosis and to encourage further research on the factors leading to <jats:italic>SIGMAR1<\/jats:italic> mutations in patients.<\/jats:p>","DOI":"10.3389\/fneur.2023.1242472","type":"journal-article","created":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T20:28:36Z","timestamp":1694636916000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["SIGMAR1 variants in ALS\u2013PD complex cases: a case report of a novel mutation and literature review"],"prefix":"10.3389","volume":"14","author":[{"given":"Haining","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Xuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"732","DOI":"10.3389\/fgene.2019.00732","article-title":"Comprehensive genetic analysis of a Hungarian amyotrophic lateral sclerosis cohort","volume":"10","author":"Tripolszki","year":"2019","journal-title":"Front Genet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1002\/ana.22534","article-title":"A mutation in sigma-1 receptor causes juvenile amyotrophic lateral sclerosis","volume":"70","author":"Al-Saif","year":"2011","journal-title":"Ann Neurol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1002\/ana.22274","article-title":"Sigma nonopioid intracellular receptor 1 mutations cause frontotemporal lobar degeneration-motor neuron disease","volume":"68","author":"Luty","year":"2010","journal-title":"Ann Neurol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s10048-015-0453-1","article-title":"In silico analysis of SIGMAR1 variant (rs4879809) segregating in a consanguineous Pakistani family showing amyotrophic lateral sclerosis without frontotemporal lobar dementia","volume":"16","author":"Ullah","year":"2015","journal-title":"Neurogenetics"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1111\/ggi.13506","article-title":"Compound heterozygote mutations in the SIGMAR1 gene in an oldest-old patient with amyotrophic lateral sclerosis","volume":"18","author":"Izumi","year":"2018","journal-title":"Geriatr Gerontol Int"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"107","DOI":"10.26502\/jppch.74050049","article-title":"Uniparental Disomy leading to a rare juvenile form of ALS","volume":"4","author":"Karasozen","year":"2020","journal-title":"J Pediatr Perinatol Child Health"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1957.e7","DOI":"10.1016\/j.neurobiolaging.2014.03.001","article-title":"Mutations in UBQLN2 and SIGMAR1 genes are rare in Korean patients with amyotrophic lateral sclerosis","volume":"35","author":"Kim","year":"2014","journal-title":"Neurobiol Aging"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/nrneurol.2014.184","article-title":"The phenotypic variability of amyotrophic lateral sclerosis","volume":"10","author":"Swinnen","year":"2014","journal-title":"Nat Rev Neurol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.ejmg.2014.01.002","article-title":"Recent progress in the genetics of motor neuron disease","volume":"57","author":"Finsterer","year":"2014","journal-title":"Eur J Med Genet"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"705575","DOI":"10.3389\/fphys.2021.705575","article-title":"Sigmar1's molecular, cellular, and biological functions in regulating cellular pathophysiology","volume":"12","author":"Aishwarya","year":"2021","journal-title":"Front Physiol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/j.tips.2010.08.007","article-title":"The sigma-1 receptor chaperone as an inter-organelle signaling modulator","volume":"31","author":"Su","year":"2010","journal-title":"Trends Pharmacol Sci"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"e21688","DOI":"10.1096\/fj.202100137R","article-title":"Novel reporters of mitochondria-associated membranes (MAM), MAMtrackers, demonstrate MAM disruption as a common pathological feature in amyotrophic lateral sclerosis","volume":"35","author":"Sakai","year":"2021","journal-title":"FASEB J"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.15252\/emmm.201606403","article-title":"Mitochondria-associated membrane collapse is a common pathomechanism in SIGMAR1- and SOD1-linked ALS","volume":"8","author":"Watanabe","year":"2016","journal-title":"EMBO Mol Med"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"e1832","DOI":"10.1038\/cddis.2015.194","article-title":"Sigma-1 receptor deficiency reduces MPTP-induced parkinsonism and death of dopaminergic neurons","volume":"6","author":"Hong","year":"2015","journal-title":"Cell Death Dis"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2023.1242472\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T20:28:39Z","timestamp":1694636919000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2023.1242472\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,13]]},"references-count":14,"alternative-id":["10.3389\/fneur.2023.1242472"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2023.1242472","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,13]]},"article-number":"1242472"}}