{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T14:05:57Z","timestamp":1740146757360,"version":"3.37.3"},"reference-count":23,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81600695"],"award-info":[{"award-number":["81600695"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Hereditary spastic paraplegias (HSPs) are a group of rare neurodegenerative disorders. HSPs are complex disorders and are clinically and genetically heterogeneous. To date, more than 80 genes or genetic loci have been reported to be responsible for HSPs in a Mendelian-dependent manner. Most recently, ubiquitin-associated protein 1 (UBAP1) has been recognized to be involved in HSP. Here, we identified novel protein truncating variants in two families with pure form of HSP. A novel deletion (c.468_469delTG) in the <jats:italic>UBAP1<\/jats:italic> gene was found in the first family, whereas a nonsense variant (c.512T&gt;G) was ascertained in the second family. The variants were confirmed in all patients but were not detected in unaffected family members. The mutations resulted in truncated proteins of UBAP1. The variants did not result in different subcellular localizations in neuro-2a cells. However, each of the two variants impaired neurite outgrowth. Taken together, our findings expand the pathogenic spectrum of <jats:italic>UBAP1<\/jats:italic> variants in HSP.<\/jats:p>","DOI":"10.1371\/journal.pone.0253871","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T17:48:19Z","timestamp":1625075299000},"page":"e0253871","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Two novel truncating variants in UBAP1 are responsible for hereditary spastic paraplegia"],"prefix":"10.1371","volume":"16","author":[{"given":"Xinchao","family":"Bian","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangying","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinbo","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongkun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangmao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3578-4920","authenticated-orcid":true,"given":"Ning","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,6,30]]},"reference":[{"issue":"3","key":"pone.0253871.ref001","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s00401-013-1115-8","article-title":"Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms","volume":"126","author":"JK Fink","year":"2013","journal-title":"Acta Neuropathol"},{"issue":"6","key":"pone.0253871.ref002","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1016\/j.ajhg.2019.05.009","article-title":"Truncating Mutations in UBAP1 Cause Hereditary Spastic Paraplegia","volume":"104","author":"MA Farazi Fard","year":"2019","journal-title":"Am J Hum Genet"},{"issue":"12","key":"pone.0253871.ref003","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1016\/S1474-4422(19)30235-2","article-title":"Hereditary spastic paraplegia: from diagnosis to emerging therapeutic approaches","volume":"18","author":"S Shribman","year":"2019","journal-title":"Lancet Neurol"},{"key":"pone.0253871.ref004","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13024-015-0064-1","article-title":"Tau missorting and spastin-induced microtubule disruption in neurodegeneration: Alzheimer Disease and Hereditary Spastic Paraplegia","volume":"10","author":"H Zempel","year":"2015","journal-title":"Mol Neurodegener"},{"issue":"1","key":"pone.0253871.ref005","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s13024-018-0269-1","article-title":"Clinical spectrum and genetic landscape for hereditary spastic paraplegias in China","volume":"13","author":"EL Dong","year":"2018","journal-title":"Mol Neurodegener"},{"key":"pone.0253871.ref006","article-title":"Hereditary spastic paraplegia overview","author":"P. Hedera","year":"2018","journal-title":"GeneReviews\u00ae"},{"key":"pone.0253871.ref007","doi-asserted-by":"crossref","first-page":"958","DOI":"10.3389\/fneur.2018.00958","article-title":"Perspectives on the Genomics of HSP Beyond Mendelian Inheritance","volume":"9","author":"DM Bis-Brewer","year":"2018","journal-title":"Front Neurol"},{"issue":"8","key":"pone.0253871.ref008","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.1093\/brain\/awz158","article-title":"Stop-gain mutations in UBAP1 cause pure autosomal-dominant spastic paraplegia","volume":"142","author":"X Lin","year":"2019","journal-title":"Brain"},{"issue":"3","key":"pone.0253871.ref009","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1002\/humu.23950","article-title":"Truncating variants in UBAP1 associated with childhood-onset nonsyndromic hereditary spastic paraplegia","volume":"41","author":"S Gu","year":"2020","journal-title":"Hum Mutat"},{"issue":"11","key":"pone.0253871.ref010","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1038\/s10038-019-0670-9","article-title":"UBAP1 mutations cause juvenile-onset hereditary spastic paraplegias (SPG80) and impair UBAP1 targeting to endosomes","volume":"64","author":"H Nan","year":"2019","journal-title":"J Hum Genet"},{"issue":"3","key":"pone.0253871.ref011","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s10048-020-00608-3","article-title":"Autosomal dominant hereditary spastic paraplegia caused by mutation of UBAP1","volume":"21","author":"J Wang","year":"2020","journal-title":"Neurogenetics"},{"issue":"12","key":"pone.0253871.ref012","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1038\/s41431-020-00720-w","article-title":"Identification of UBAP1 mutations in juvenile hereditary spastic paraplegia in the 100,000 Genomes Project","volume":"28","author":"T Bourinaris","year":"2020","journal-title":"European Journal of Human Genetics"},{"issue":"Pt 3","key":"pone.0253871.ref013","first-page":"663","article-title":"The molecular basis for selective assembly of the UBAP1-containing endosome-specific ESCRT-I complex","volume":"127","author":"L Wunderley","year":"2014","journal-title":"J Cell Sci"},{"issue":"3","key":"pone.0253871.ref014","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.str.2011.12.013","article-title":"The UBAP1 subunit of ESCRT-I interacts with ubiquitin via a SOUBA domain","volume":"20","author":"M Agromayor","year":"2012","journal-title":"Structure"},{"issue":"10","key":"pone.0253871.ref015","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/s004320100252","article-title":"Isolation and characterization of a novel cDNA, UBAP1, derived from the tumor suppressor locus in human chromosome 9p21-22","volume":"127","author":"J Qian","year":"2001","journal-title":"J Cancer Res Clin Oncol"},{"issue":"17","key":"pone.0253871.ref016","doi-asserted-by":"crossref","first-page":"6308","DOI":"10.1073\/pnas.0707601105","article-title":"The Bro1-related protein HD-PTP\/PTPN23 is required for endosomal cargo sorting and multivesicular body morphogenesis","volume":"105","author":"A Doyotte","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"12","key":"pone.0253871.ref017","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1016\/j.str.2016.10.006","article-title":"Structural Basis for Selective Interaction between the ESCRT Regulator HD-PTP and UBAP1","volume":"24","author":"D Gahloth","year":"2016","journal-title":"Structure"},{"issue":"14","key":"pone.0253871.ref018","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.cub.2011.06.028","article-title":"UBAP1 is a component of an endosome-specific ESCRT-I complex that is essential for MVB sorting","volume":"21","author":"F Stefani","year":"2011","journal-title":"Curr Biol"},{"issue":"7","key":"pone.0253871.ref019","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1136\/jmedgenet-2012-100742","article-title":"A founder mutation in Vps37A causes autosomal recessive complex hereditary spastic paraparesis","volume":"49","author":"Y Zivony-Elboum","year":"2012","journal-title":"J Med Genet"},{"issue":"11","key":"pone.0253871.ref020","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1093\/hmg\/ddw082","article-title":"Heterozygous KIDINS220\/ARMS nonsense variants cause spastic paraplegia, intellectual disability, nystagmus, and obesity","volume":"25","author":"DJ Josifova","year":"2016","journal-title":"Hum Mol Genet"},{"issue":"19","key":"pone.0253871.ref021","doi-asserted-by":"crossref","first-page":"3792","DOI":"10.1093\/hmg\/ddx263","article-title":"Homozygous KIDINS220 loss-of-function variants in fetuses with cerebral ventriculomegaly and limb contractures","volume":"26","author":"IL Mero","year":"2017","journal-title":"Hum Mol Genet"},{"issue":"12","key":"pone.0253871.ref022","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/S1474-4422(08)70258-8","article-title":"Hereditary spastic paraplegia: clinical features and pathogenetic mechanisms","volume":"7","author":"S Salinas","year":"2008","journal-title":"Lancet Neurol"},{"issue":"7","key":"pone.0253871.ref023","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1002\/jcb.24100","article-title":"Role of spastin and protrudin in neurite outgrowth","volume":"113","author":"C Zhang","year":"2012","journal-title":"J Cell Biochem"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0253871","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T17:48:42Z","timestamp":1625075322000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0253871"}},"subtitle":[],"editor":[{"given":"Mathias","family":"Toft","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,6,30]]},"references-count":23,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0253871","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2021,6,30]]}}}