{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:23:01Z","timestamp":1792790581411,"version":"4.5.0"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["338446"],"award-info":[{"award-number":["338446"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Uolevi M\u00e4ki Foundation and the Competitive State Research Financing of the Expert Responsibility Area of Oulu University Hospital","id":[{"id":"https:\/\/ror.org\/045ney286","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Hum Genet"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Jones syndrome is a rare dominantly inherited syndrome characterized by gingival fibromatosis and progressive sensorineural hearing loss becoming symptomatic in the second decade of life. Here, we report a father and his two daughters presenting with a typical Jones syndrome (OMIM %135550) phenotype. Exome sequencing identified a repressor element 1-silencing transcription factor (\n                    <jats:italic>REST<\/jats:italic>\n                    , OMIM *600571) (NM_005612.5) c.2670_2673del p.(Glu891Profs*6) heterozygous variant segregating with Jones syndrome in the family. We review the clinical data from all previously published patients with Jones syndrome and previously published patients with pathogenic\n                    <jats:italic>REST<\/jats:italic>\n                    variants associated with gingival fibromatosis or sensorineural hearing loss. This study suggests that pathogenic\n                    <jats:italic>REST<\/jats:italic>\n                    variants cause Jones syndrome.\n                  <\/jats:p>","DOI":"10.1038\/s41431-022-01258-9","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T22:02:43Z","timestamp":1670882563000},"page":"469-473","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Pathogenic REST variant causing Jones syndrome and a review of the literature"],"prefix":"10.1038","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2760-7059","authenticated-orcid":false,"given":"Elisa","family":"Rahikkala","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4777-3943","authenticated-orcid":false,"given":"Johanna","family":"Julku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sari","family":"Koskinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommi","family":"Keski-Filppula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5013-4806","authenticated-orcid":false,"given":"Stephanie","family":"Weissgraeber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9544-1877","authenticated-orcid":false,"given":"Aida M.","family":"Bertoli-Avella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanna","family":"H\u00e4kli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8072-699X","authenticated-orcid":false,"given":"Minna","family":"Kraatari-Tiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,12,13]]},"reference":[{"key":"1258_CR1","first-page":"195","volume":"13","author":"G Jones","year":"1977","unstructured":"Jones G, Wilroy RS, McHaney V. Familial gingival fibromatosis associated with progressive deafness in five generations of a family. Birth Defects Orig Artic Ser. 1977;13:195\u2013201.","journal-title":"Birth Defects Orig Artic Ser"},{"key":"1258_CR2","first-page":"62","volume":"17","author":"R Da","year":"2016","unstructured":"Da R, Singh S, Gupta I, Gopal S. Gingival enlargement in a case of variant Jones Syndrome: a case report. J Dent. 2016;17:62\u20136.","journal-title":"J Dent"},{"key":"1258_CR3","doi-asserted-by":"publisher","unstructured":"Gita B, Chandrasekaran S, Manoharan P, Dembla G. Idiopathic gingival fibromatosis associated with progressive hearing loss: a nonfamilial variant of Jones syndrome. Contemp Clin Dent. 2014; https:\/\/doi.org\/10.4103\/0976-237X.132387.","DOI":"10.4103\/0976-237X.132387"},{"key":"1258_CR4","doi-asserted-by":"publisher","unstructured":"Hartsfield JK, Bixler D, Hazen RH. Gingival fibromatosis with sensorineural hearing loss: an autosomal dominant trait. Am J Med Genet. 1985; https:\/\/doi.org\/10.1002\/ajmg.1320220323.","DOI":"10.1002\/ajmg.1320220323"},{"key":"1258_CR5","first-page":"213","volume":"15","author":"O Kasabo\u011flu","year":"2004","unstructured":"Kasabo\u011flu O, T\u00fcmer C, Balci S. Hereditary gingival fibromatosis and sensorineural hearing loss in a 42-year-old man with Jones syndrome. Genet Couns. 2004;15:213\u20138.","journal-title":"Genet Couns"},{"key":"1258_CR6","doi-asserted-by":"publisher","unstructured":"Manyisa N, Schrauwen I, de Souza Rios LA, Mowla S, Tekendo-Ngongang C, Popel K, et al. A monoallelic variant in REST is associated with non-syndromic autosomal dominant hearing impairment in a South African family. Genes. 2021; https:\/\/doi.org\/10.3390\/genes12111765.","DOI":"10.3390\/genes12111765"},{"key":"1258_CR7","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/j.cell.2018.06.004","volume":"174","author":"Y Nakano","year":"2018","unstructured":"Nakano Y, Kelly MC, Rehman AU, Boger ET, Morell RJ, Kelley MW, et al. Defects in the alternative splicing-dependent regulation of REST cause deafness. Cell 2018;174:536\u2013548. https:\/\/doi.org\/10.1016\/j.cell.2018.06.004.","journal-title":"Cell"},{"key":"1258_CR8","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.ajhg.2017.06.006","volume":"101","author":"Y Bayram","year":"2017","unstructured":"Bayram Y, White JJ, Elcioglu N, Cho MT, Zadeh N, Gedikbasi A, et al. RESt final-exon-truncating mutations cause hereditary gingival fibromatosis. Am J Hum Genet. 2017;101:149\u2013156. https:\/\/doi.org\/10.1016\/j.ajhg.2017.06.006.","journal-title":"Am J Hum Genet"},{"key":"1258_CR9","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1177\/0022034521996620","volume":"100","author":"JT Chen","year":"2021","unstructured":"Chen JT, Lin CH, Huang HW, Wang YP, Kao PC, Yang TP, et al. Novel REST truncation mutations causing hereditary gingival fibromatosis. J Dent Res. 2021;100:868\u2013874. https:\/\/doi.org\/10.1177\/0022034521996620.","journal-title":"J Dent Res"},{"key":"1258_CR10","doi-asserted-by":"publisher","unstructured":"Machado RA, de Andrade RS, P\u00eago SPB, Krepischi ACV, Coletta RD, Martelli-J\u00fanior H. New evidences of genetic heterogeneity of causing hereditary gingival fibromatosis and ALK and CD36 as new candidate genes. J Periodontol. 2022; https:\/\/doi.org\/10.1002\/JPER.22-0219.","DOI":"10.1002\/JPER.22-0219"},{"key":"1258_CR11","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1038\/ng.3440","volume":"47","author":"SS Mahamdallie","year":"2015","unstructured":"Mahamdallie SS, Hanks S, Karlin KL, Zachariou A, Perdeaux ER, Ruark E, et al. Mutations in the transcriptional repressor REST predispose to Wilms tumor. Nat Genet. 2015;47:1471\u20134. https:\/\/doi.org\/10.1038\/ng.3440.","journal-title":"Nat Genet"},{"key":"1258_CR12","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405\u201324. https:\/\/doi.org\/10.1038\/gim.2015.30.","journal-title":"Genet Med"},{"key":"1258_CR13","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1111\/j.1399-0004.2008.00966.x","volume":"73","author":"LM Peters","year":"2008","unstructured":"Peters LM, Fridell RA, Boger ET, San Agustin TB, Madeo AC, Griffith AJ, et al. A locus for autosomal dominant progressive non-syndromic hearing loss, DFNA27, is on chromosome 4q12-13.1. Clin Genet. 2008;73:367\u201372. https:\/\/doi.org\/10.1111\/j.1399-0004.2008.00966.x.","journal-title":"Clin Genet"},{"key":"1258_CR14","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-04774-0","volume":"13","author":"H Li","year":"2022","unstructured":"Li H. Downregulation of REST in the cochlea contributes to age-related hearing loss via the p53 apoptosis pathway. Cell Death Dis. 2022;13:343 https:\/\/doi.org\/10.1038\/s41419-022-04774-0.","journal-title":"Cell Death Dis"},{"key":"1258_CR15","doi-asserted-by":"publisher","first-page":"D480","DOI":"10.1093\/nar\/gkaa1100","volume":"49","author":"UniProt Consortium.","year":"2021","unstructured":"UniProt Consortium. UniProt: the universal protein knowledgebase in 2021. Nucleic Acids Res. 2021;49:D480\u2013D489. https:\/\/doi.org\/10.1093\/nar\/gkaa1100.","journal-title":"Nucleic Acids Res"},{"key":"1258_CR16","doi-asserted-by":"publisher","first-page":"39","DOI":"10.3390\/diseases7020039","volume":"7","author":"L Roman-Malo","year":"2019","unstructured":"Roman-Malo L, Bullon B, de Miguel M, Bullon P. Fibroblasts collagen production and histological alterations in hereditary gingival fibromatosis. Diseases. 2019;7:39 https:\/\/doi.org\/10.3390\/diseases7020039.","journal-title":"Diseases."},{"key":"1258_CR17","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1902\/jop.2010.100510","volume":"82","author":"LM Sobral","year":"2011","unstructured":"Sobral LM, Montan PF, Zecchin KG, Martelli-Junior H, Vargas PA, Graner E, et al. Smad7 blocks transforming growth factor-\u03b21-induced gingival fibroblast-myofibroblast transition via inhibitory regulation of Smad2 and connective tissue growth factor. J Periodontol. 2011;82:642\u201351. https:\/\/doi.org\/10.1902\/jop.2010.100510.","journal-title":"J Periodontol"}],"container-title":["European Journal of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41431-022-01258-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41431-022-01258-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41431-022-01258-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T10:08:39Z","timestamp":1682503719000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41431-022-01258-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,13]]},"references-count":17,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["1258"],"URL":"https:\/\/doi.org\/10.1038\/s41431-022-01258-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-2007051\/v1","asserted-by":"object"}]},"ISSN":["1018-4813","1476-5438"],"issn-type":[{"value":"1018-4813","type":"print"},{"value":"1476-5438","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,13]]},"assertion":[{"value":"28 August 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 October 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 November 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 December 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"SW, AMBA are employees of CENTOGENE GmbH. The authors declare no conflicts of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Written informed consent was obtained from all the patients and unaffected siblings participating in the study. Written informed consent was obtained to publish patient photos. The study was approved by the Ethics Committee of the Northern Ostrobothnia Hospital District (Eettmk \u00a7 186, 17\/08\/2020).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics"}}]}}