{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T08:31:20Z","timestamp":1786350680295,"version":"build-2736575974"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurogenetics"],"DOI":"10.1007\/s10048-026-00924-0","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T08:11:08Z","timestamp":1786349468000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical significance of SQSTM1 variants in ALS: report of p.Arg119Cys and literature review"],"prefix":"10.1007","volume":"27","author":[{"given":"Boyang","family":"Su","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyue","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuli","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhong","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"issue":"2","key":"924_CR1","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1056\/NEJMra1603471","volume":"377","author":"RH Brown","year":"2017","unstructured":"Brown RH, Al-Chalabi A (2017) Amyotrophic Lateral Sclerosis. N Engl J Med 377(2):162\u2013172","journal-title":"N Engl J Med"},{"issue":"10360","key":"924_CR2","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1016\/S0140-6736(22)01272-7","volume":"400","author":"EL Feldman","year":"2022","unstructured":"Feldman EL et al (2022) Amyotrophic lateral sclerosis. Lancet 400(10360):1363\u20131380","journal-title":"Lancet"},{"issue":"7676","key":"924_CR3","doi-asserted-by":"publisher","first-page":"S105","DOI":"10.1038\/550S105a","volume":"550","author":"B Owens","year":"2017","unstructured":"Owens B (2017) Amyotrophic lateral sclerosis. Nature 550(7676):S105","journal-title":"Nature"},{"key":"924_CR4","doi-asserted-by":"crossref","unstructured":"Gagliardi D et al (2026) High Prevalence of SOD1 Pathogenic Variants in the UK Biobank: Implications for Early Intervention in Amyotrophic Lateral Sclerosis. Ann Neurol","DOI":"10.1101\/2025.06.12.25329421"},{"issue":"13\u201315","key":"924_CR5","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1177\/15230864251395963","volume":"43","author":"D Zhu","year":"2025","unstructured":"Zhu D et al (2025) SQSTM1\/p62 Post-Translational Modifications and Reverse Processes Modulate Disease Pathogenesis via KEAP1-NRF2 Signaling and Selective Autophagy. Antioxid Redox Signal 43(13\u201315):745\u2013764","journal-title":"Antioxid Redox Signal"},{"key":"924_CR6","doi-asserted-by":"crossref","unstructured":"Kim YJ et al (2026) The Roles of SQSTM1\/p62 in Selective Autophagy and Oncogenic Signaling. Int J Mol Sci 27(5):2342","DOI":"10.3390\/ijms27052342"},{"key":"924_CR7","doi-asserted-by":"publisher","first-page":"105653","DOI":"10.1016\/j.nbd.2022.105653","volume":"166","author":"JM Davidson","year":"2022","unstructured":"Davidson JM, Chung RS, Lee A (2022) The converging roles of sequestosome-1\/p62 in the molecular pathways of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Neurobiol Dis 166:105653","journal-title":"Neurobiol Dis"},{"issue":"11","key":"924_CR8","doi-asserted-by":"publisher","first-page":"1440","DOI":"10.1001\/archneurol.2011.250","volume":"68","author":"F Fecto","year":"2011","unstructured":"Fecto F et al (2011) SQSTM1 mutations in familial and sporadic amyotrophic lateral sclerosis. Arch Neurol 68(11):1440\u20131446","journal-title":"Arch Neurol"},{"issue":"10","key":"924_CR9","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1136\/jmg-2023-109569","volume":"61","author":"S Wang","year":"2024","unstructured":"Wang S et al (2024) Genotype-phenotype correlation of SQSTM1 variants in patients with amyotrophic lateral sclerosis. J Med Genet 61(10):966\u2013972","journal-title":"J Med Genet"},{"key":"924_CR10","doi-asserted-by":"publisher","first-page":"139e9","DOI":"10.1016\/j.neurobiolaging.2019.10.018","volume":"87","author":"R Yilmaz","year":"2020","unstructured":"Yilmaz R et al (2020) SQSTM1\/p62 variants in 486 patients with familial ALS from Germany and Sweden. Neurobiol Aging 87:139e9\u2013139e15","journal-title":"Neurobiol Aging"},{"key":"924_CR11","doi-asserted-by":"crossref","unstructured":"Kartanou C et al (2026) Unraveling the genetic landscape of ALS in Greece: identification of known and novel causative variants in a 353-patient cohort. Amyotroph Lateral Scler Front Degener 27(3-4):318\u2013327","DOI":"10.1080\/21678421.2025.2582828"},{"key":"924_CR12","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.neuroscience.2025.07.011","volume":"581","author":"N Singh","year":"2025","unstructured":"Singh N, Mishra D, Gomes J (2025) Deleterious Sequestosome 1 mutations G262R and P438L in amyotrophic lateral sclerosis cause autophagy and oxidative stress imbalance. Neuroscience 581:233\u2013246","journal-title":"Neuroscience"},{"key":"924_CR13","doi-asserted-by":"crossref","unstructured":"Lipskerov F, Cohen-Kaplan V, Ciechanover A (2026) Precise mapping of the proteasome interaction region (PIR) of p62\/SQSTM1: decoupling condensate formation from proteasome recruitment. Cells 15(4):335","DOI":"10.3390\/cells15040335"},{"issue":"3","key":"924_CR14","doi-asserted-by":"publisher","first-page":"726e7","DOI":"10.1016\/j.neurobiolaging.2013.09.008","volume":"35","author":"Y Chen","year":"2014","unstructured":"Chen Y et al (2014) SQSTM1 mutations in Han Chinese populations with sporadic amyotrophic lateral sclerosis. Neurobiol Aging 35(3):726e7\u2013726e9","journal-title":"Neurobiol Aging"},{"issue":"15","key":"924_CR15","doi-asserted-by":"publisher","first-page":"1556","DOI":"10.1212\/WNL.0b013e31826e25df","volume":"79","author":"E Rubino","year":"2012","unstructured":"Rubino E et al (2012) SQSTM1 mutations in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Neurology 79(15):1556\u20131562","journal-title":"Neurology"},{"issue":"5\u20136","key":"924_CR16","doi-asserted-by":"publisher","first-page":"378","DOI":"10.3109\/21678421.2015.1009466","volume":"16","author":"Y Yang","year":"2015","unstructured":"Yang Y et al (2015) Six SQSTM1 mutations in a Chinese amyotrophic lateral sclerosis cohort. Amyotroph Lateral Scler Frontotemporal Degener 16(5\u20136):378\u2013384","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"issue":"4","key":"924_CR17","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1007\/s00401-013-1090-0","volume":"125","author":"E Teyssou","year":"2013","unstructured":"Teyssou E et al (2013) Mutations in SQSTM1 encoding p62 in amyotrophic lateral sclerosis: genetics and neuropathology. Acta Neuropathol 125(4):511\u2013522","journal-title":"Acta Neuropathol"},{"issue":"8","key":"924_CR18","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1212\/WNL.0000000000001864","volume":"85","author":"RC Bucelli","year":"2015","unstructured":"Bucelli RC et al (2015) SQSTM1 splice site mutation in distal myopathy with rimmed vacuoles. Neurology 85(8):665\u2013674","journal-title":"Neurology"},{"issue":"4","key":"924_CR19","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1038\/ejhg.2013.184","volume":"22","author":"CT Kwok","year":"2014","unstructured":"Kwok CT, Morris A, de Belleroche JS (2014) Sequestosome-1 (SQSTM1) sequence variants in ALS cases in the UK: prevalence and coexistence of SQSTM1 mutations in ALS kindred with PDB. Eur J Hum Genet 22(4):492\u2013496","journal-title":"Eur J Hum Genet"},{"issue":"3","key":"924_CR20","doi-asserted-by":"publisher","first-page":"173","DOI":"10.24425\/fmc.2025.156692","volume":"65","author":"K \u017bur-Wyrozumska","year":"2025","unstructured":"\u017bur-Wyrozumska K (2025) A case of an ALS patient with an SQSTM1 mutation - implications for the p62\/NF-\u03baB\/Nrf2\/autophagy pathways in the selection of individualised therapeutic strategies: a preliminary report. Folia Med Cracov 65(3):173\u2013183","journal-title":"Folia Med Cracov"},{"key":"924_CR21","doi-asserted-by":"crossref","unstructured":"Kim HJ et al (2016) Identification of mutations in Korean patients with amyotrophic lateral sclerosis using multigene panel testing. Neurobiol Aging 37:209.e9-209.e16","DOI":"10.1016\/j.neurobiolaging.2015.09.012"},{"issue":"5","key":"924_CR22","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1212\/WNL.0b013e31827f0fe5","volume":"80","author":"M Hirano","year":"2013","unstructured":"Hirano M et al (2013) Mutations in the gene encoding p62 in Japanese patients with amyotrophic lateral sclerosis. Neurology 80(5):458\u2013463","journal-title":"Neurology"},{"issue":"3","key":"924_CR23","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1007\/s00401-013-1150-5","volume":"126","author":"H Shimizu","year":"2013","unstructured":"Shimizu H et al (2013) Sporadic ALS with compound heterozygous mutations in the SQSTM1 gene. Acta Neuropathol 126(3):453\u2013459","journal-title":"Acta Neuropathol"},{"issue":"3","key":"924_CR24","first-page":"201","volume":"55","author":"Mingxing","year":"2021","unstructured":"Mingxing, Lin et al (2021) The phnotype of SQSTM1 mutation of amyotrophic lateral sclerosis. J Fujian Med Univ 55(3):201\u2013209","journal-title":"J Fujian Med Univ"},{"issue":"4","key":"924_CR25","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1007\/s00415-020-10283-x","volume":"268","author":"W Li","year":"2021","unstructured":"Li W et al (2021) SQSTM1 variant in disorders of the frontotemporal dementia-amyotrophic lateral sclerosis spectrum: identification of a novel heterozygous variant and a review of the literature. J Neurol 268(4):1351\u20131357","journal-title":"J Neurol"},{"issue":"3","key":"924_CR26","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1007\/s00401-014-1298-7","volume":"128","author":"J van der Zee","year":"2014","unstructured":"van der Zee J et al (2014) Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration. Acta Neuropathol 128(3):397\u2013410","journal-title":"Acta Neuropathol"},{"issue":"1","key":"924_CR27","doi-asserted-by":"publisher","first-page":"e4840","DOI":"10.1002\/pro.4840","volume":"33","author":"L Alcober-Boquet","year":"2024","unstructured":"Alcober-Boquet L et al (2024) The PB1 and the ZZ domain of the autophagy receptor p62\/SQSTM1 regulate the interaction of p62\/SQSTM1 with the autophagosome protein LC3B. Protein Sci 33(1):e4840","journal-title":"Protein Sci"},{"issue":"2","key":"924_CR28","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.febslet.2006.12.027","volume":"581","author":"ML Seibenhener","year":"2007","unstructured":"Seibenhener ML, Geetha T, Wooten MW (2007) Sequestosome 1\/p62\u2013more than just a scaffold. FEBS Lett 581(2):175\u2013179","journal-title":"FEBS Lett"},{"issue":"2","key":"924_CR29","doi-asserted-by":"publisher","first-page":"138","DOI":"10.4161\/auto.2.2.2405","volume":"2","author":"G Bj\u00f8rk\u00f8y","year":"2006","unstructured":"Bj\u00f8rk\u00f8y G, Lamark T, Johansen T (2006) p62\/SQSTM1: a missing link between protein aggregates and the autophagy machinery. Autophagy 2(2):138\u2013139","journal-title":"Autophagy"},{"issue":"6","key":"924_CR30","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1016\/j.cell.2009.05.023","volume":"137","author":"J Moscat","year":"2009","unstructured":"Moscat J, Diaz-Meco MT (2009) p62 at the crossroads of autophagy, apoptosis, and cancer. Cell 137(6):1001\u20131004","journal-title":"Cell"},{"issue":"24","key":"924_CR31","doi-asserted-by":"publisher","first-page":"4672","DOI":"10.1111\/febs.13540","volume":"282","author":"Y Katsuragi","year":"2015","unstructured":"Katsuragi Y, Ichimura Y, Komatsu M (2015) p62\/SQSTM1 functions as a signaling hub and an autophagy adaptor. Febs j 282(24):4672\u20134678","journal-title":"Febs j"},{"issue":"5","key":"924_CR32","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1089\/dna.2012.1915","volume":"32","author":"X Lin","year":"2013","unstructured":"Lin X et al (2013) Interaction domains of p62: a bridge between p62 and selective autophagy. DNA Cell Biol 32(5):220\u2013227","journal-title":"DNA Cell Biol"},{"issue":"4","key":"924_CR33","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/S1474-4422(12)70043-1","volume":"11","author":"E Majounie","year":"2012","unstructured":"Majounie E et al (2012) Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. Lancet Neurol 11(4):323\u2013330","journal-title":"Lancet Neurol"},{"issue":"1","key":"924_CR34","first-page":"2","volume":"42","author":"E Iannibelli","year":"2023","unstructured":"Iannibelli E et al (2023) VCP-related myopathy: a case series and a review of literature. Acta Myol 42(1):2\u201313","journal-title":"Acta Myol"},{"issue":"3","key":"924_CR35","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1001\/jamaneurol.2019.3924","volume":"77","author":"SA Glasmacher","year":"2020","unstructured":"Glasmacher SA et al (2020) Survival and Prognostic Factors in C9orf72 Repeat Expansion Carriers: A Systematic Review and Meta-analysis. JAMA Neurol 77(3):367\u2013376","journal-title":"JAMA Neurol"},{"key":"924_CR36","doi-asserted-by":"publisher","first-page":"105156","DOI":"10.1016\/j.nbd.2020.105156","volume":"147","author":"A Shatunov","year":"2021","unstructured":"Shatunov A, Al-Chalabi A (2021) The genetic architecture of ALS. Neurobiol Dis 147:105156","journal-title":"Neurobiol Dis"},{"issue":"1","key":"924_CR37","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s11910-996-0008-9","volume":"6","author":"PM Andersen","year":"2006","unstructured":"Andersen PM (2006) Amyotrophic lateral sclerosis associated with mutations in the CuZn superoxide dismutase gene. Curr Neurol Neurosci Rep 6(1):37\u201346","journal-title":"Curr Neurol Neurosci Rep"},{"issue":"4","key":"924_CR38","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nrn3430","volume":"14","author":"W Robberecht","year":"2013","unstructured":"Robberecht W, Philips T (2013) The changing scene of amyotrophic lateral sclerosis. Nat Rev Neurosci 14(4):248\u2013264","journal-title":"Nat Rev Neurosci"},{"issue":"5","key":"924_CR39","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1038\/ng.132","volume":"40","author":"E Kabashi","year":"2008","unstructured":"Kabashi E et al (2008) TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet 40(5):572\u2013574","journal-title":"Nat Genet"},{"key":"924_CR40","doi-asserted-by":"crossref","unstructured":"Roy \u00c9 et al (2026) Oligogenic variants in NEK1 and ATXN2 in amyotrophic lateral sclerosis: report of two cases and review of the literature. Amyotroph Lateral Scler Frontotemporal Degener","DOI":"10.1080\/21678421.2026.2685158"},{"issue":"10","key":"924_CR41","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1136\/jnnp-2024-335364","volume":"96","author":"A Iacoangeli","year":"2025","unstructured":"Iacoangeli A et al (2025) Oligogenic structure of amyotrophic lateral sclerosis has genetic testing, counselling and therapeutic implications. J Neurol Neurosurg Psychiatry 96(10):928\u2013936","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"924_CR42","doi-asserted-by":"publisher","first-page":"1438207","DOI":"10.3389\/fneur.2025.1438207","volume":"16","author":"Y Wang","year":"2025","unstructured":"Wang Y et al (2025) Combined impact of CHCHD10 p.Gly66Val and three other variants suggests oligogenic contributions to ALS. Front Neurol 16:1438207","journal-title":"Front Neurol"},{"issue":"4","key":"924_CR43","doi-asserted-by":"publisher","first-page":"588","DOI":"10.4161\/auto.27710","volume":"10","author":"X Zhang","year":"2014","unstructured":"Zhang X et al (2014) MTOR-independent, autophagic enhancer trehalose prolongs motor neuron survival and ameliorates the autophagic flux defect in a mouse model of amyotrophic lateral sclerosis. Autophagy 10(4):588\u2013602","journal-title":"Autophagy"},{"issue":"6","key":"924_CR44","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1016\/S1474-4422(25)00173-5","volume":"24","author":"Safety","year":"2025","unstructured":"Safety (2025) efficacy of trehalose in amyotrophic lateral sclerosis (HEALEY ALS Platform Trial): an adaptive, phase 2\/3, double-blind, randomised, placebo-controlled trial. Lancet Neurol 24(6):500\u2013511and","journal-title":"Lancet Neurol"},{"issue":"1","key":"924_CR45","doi-asserted-by":"publisher","first-page":"4970","DOI":"10.1038\/s41467-023-40734-8","volume":"14","author":"J Mandrioli","year":"2023","unstructured":"Mandrioli J et al (2023) Randomized, double-blind, placebo-controlled trial of rapamycin in amyotrophic lateral sclerosis. Nat Commun 14(1):4970","journal-title":"Nat Commun"},{"issue":"6","key":"924_CR46","doi-asserted-by":"publisher","first-page":"1682","DOI":"10.1093\/hmg\/ddu580","volume":"24","author":"S Lattante","year":"2015","unstructured":"Lattante S et al (2015) Sqstm1 knock-down causes a locomotor phenotype ameliorated by rapamycin in a zebrafish model of ALS\/FTLD. Hum Mol Genet 24(6):1682\u20131690","journal-title":"Hum Mol Genet"},{"key":"924_CR47","doi-asserted-by":"crossref","unstructured":"Park DY et al (2025) Targeted degradation of pathogenic TDP-43 proteins in amyotrophic lateral sclerosis using the AUTOTAC platform. bioRxiv","DOI":"10.1101\/2025.08.31.673396"}],"container-title":["Neurogenetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10048-026-00924-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10048-026-00924-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10048-026-00924-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T08:11:12Z","timestamp":1786349472000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10048-026-00924-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["924"],"URL":"https:\/\/doi.org\/10.1007\/s10048-026-00924-0","relation":{},"ISSN":["1364-6753"],"issn-type":[{"value":"1364-6753","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]},"assertion":[{"value":"8 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Beijing Tsinghua Chuangguang Hospital (Approval No.26504-6-01). Written informed consent was obtained from the patient and his family members for the publication of clinical data and genetic testing results.","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","label":"Competing interest","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"55"}}