{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:46:28Z","timestamp":1787071588487,"version":"build-2736575974"},"reference-count":13,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"\n Mutations in the\n SQSTM1<\/jats:italic>\n gene have recently been identified as rare causes of progressive childhood neurodegenerative diseases. To date, only 27 cases have been reported, with 11 different mutations affecting\n SQSTM1<\/jats:italic>\n . Here, we describe two new cases of progressive childhood-onset cerebellar ataxia with gaze palsy, in whom clinical exome sequencing identified a novel pathogenic variant. The first patient was a 12-year-old boy of Iraqi and Iranian descent, who presented with a 3-year history of recurrent falls, swaying while walking, and difficulties with writing and speech. Physical examination revealed frozen eye movements, gait ataxia, and dysarthria. The second patient was a 9-year-old Iranian boy, who developed involuntary movements, gait instability, and tremor at the age of 8 years. On examination, cerebellar ataxia and dysarthria were observed. In both cases, initial workup was unremarkable, but whole-exome sequencing revealed a novel homozygous pathogenic truncating mutation,\n SQSTM1<\/jats:italic>\n (c.838G>T, p. Glu280Ter). During 2 years of follow-up, the second patient developed gaze palsy. This report highlights the importance of considering\n SQSTM1<\/jats:italic>\n mutations in the differential diagnosis of patients presenting with both cerebellar ataxia and ophthalmological manifestations.\n <\/jats:p>","DOI":"10.4103\/abr.abr_308_24","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T10:00:15Z","timestamp":1761904815000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Novel SQSTM1 (c.838G>T) Mutation Identified in Two Unrelated Cases of Cerebellar Ataxia and Gaze Palsy"],"prefix":"10.4103","volume":"14","author":[{"given":"Neda","family":"Hosseini Moshkenani","sequence":"first","affiliation":[{"name":"Department of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azin","family":"Momeni","sequence":"additional","affiliation":[{"name":"Department of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Bahreini","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,10]]},"reference":[{"key":"R1-20251130","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.febslet.2006.12.027","article-title":"Sequestosome 1\/p62--more than just a scaffold","volume":"581","author":"Seibenhener","year":"2007","journal-title":"FEBS Lett"},{"key":"R2-20251130","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.yexcr.2014.01.020","article-title":"SQSTM1 mutations--bridging paget disease of bone and ALS\/FTLD","volume":"325","author":"Rea","year":"2014","journal-title":"Exp Cell Res"},{"key":"R3-20251130","doi-asserted-by":"crossref","first-page":"e0128984","DOI":"10.1371\/journal.pone.0128984","article-title":"Polymorphisms in autophagy genes are associated with paget disease of bone","volume":"10","author":"Usategui-Mart\u00edn","year":"2015","journal-title":"PLoS One"},{"key":"R4-20251130","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1080\/15548627.2016.1170257","article-title":"Defective recognition of LC3B by mutant SQSTM1\/p62 implicates impairment of autophagy as a pathogenic mechanism in ALS-FTLD","volume":"12","author":"Goode","year":"2016","journal-title":"Autophagy Rep"},{"key":"R5-20251130","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.mcn.2015.01.002","article-title":"Autophagy receptor defects and ALS-FTLD","volume":"66","author":"Majcher","year":"2015","journal-title":"Mol Cell Neurosci"},{"key":"R6-20251130","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.parkreldis.2018.12.031","article-title":"Beyond dystonia and ataxia: Expanding the phenotype of SQSTM1 mutations","volume":"62","author":"Z\u00fa\u00f1iga-Ram\u00edrez","year":"2019","journal-title":"Parkinsonism Relat Disord"},{"key":"R7-20251130","doi-asserted-by":"crossref","first-page":"e1543","DOI":"10.1002\/mgg3.1543","article-title":"SQSTM1 mutation: Description of the first Tunisian case and literature review","volume":"8","author":"Akkari","year":"2020","journal-title":"Mol Genet Genomic Med"},{"key":"R8-20251130","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1001\/jamaneurol.2019.1534","article-title":"Diagnostic value of cerebrospinal fluid neurofilament light protein in neurology: A systematic review and meta-analysis","volume":"76","author":"Bridel","year":"2019","journal-title":"JAMA Neurol"},{"key":"R9-20251130","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/aps.2013.12","article-title":"Bcl-2-dependent upregulation of autophagy by sequestosome 1\/p62 in vitro","volume":"34","author":"Zhou","year":"2013","journal-title":"Acta Pharmacol Sin"},{"key":"R10-20251130","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1080\/13816810.2019.1666414","article-title":"Homozygous sequestosome 1 (SQSTM1) mutation: A rare cause for childhood-onset progressive cerebellar ataxia with vertical gaze palsy","volume":"40","author":"Vedartham","year":"2019","journal-title":"Ophthalmic Genet"},{"key":"R11-20251130","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.ajhg.2016.06.026","article-title":"Absence of the autophagy adaptor SQSTM1\/p62 causes childhood-onset neurodegeneration with ataxia, dystonia, and gaze palsy","volume":"99","author":"Haack","year":"2016","journal-title":"Am J Hum Genet"},{"key":"R12-20251130","doi-asserted-by":"crossref","first-page":"e6203","DOI":"10.1002\/ccr3.6203","article-title":"First report of novel mutation (c. 790del) on SQSTM1 gene on a family with childhood onset of progressive cerebellar ataxia with vertical gaze palsy","volume":"10","author":"Jalali","year":"2022","journal-title":"Clin Case Rep"},{"key":"R13-20251130","doi-asserted-by":"crossref","first-page":"e319","DOI":"10.1212\/WNL.0000000000005869","article-title":"Biallelic SQSTM1 mutations in early-onset, variably progressive neurodegeneration","volume":"91","author":"Muto","year":"2018","journal-title":"Neurology"}],"container-title":["Advanced Biomedical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/abr.abr_308_24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:49:00Z","timestamp":1787068140000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/abr.abr_308_24"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":13,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.4103\/abr.abr_308_24","relation":{},"ISSN":["2277-9175"],"issn-type":[{"value":"2277-9175","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"2024-07-06","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-09","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}