{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T02:34:20Z","timestamp":1787884460646,"version":"build-2784847793"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"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. Genet."],"abstract":"<jats:p>Cyclic neutropenia (CyN) is a rare, <jats:italic>ELANE<\/jats:italic>-related neutropenia. Oral manifestations are among the initial signs of CyN and an important reason that leads patients to seek professional help. This case report describes a 12-year-old girl with recurrent oral ulcers, severe chronic periodontitis, and pathological tooth migration as the initial and main clinical symptoms of CyN. Two novel mutations in <jats:italic>ELANE<\/jats:italic>, c.180T&amp;gt;G (p.I60M) and c.182C&amp;gt;G (p.A61G) associated with CyN were observed. Bioinformatics research indicated lower stability and impaired molecular linkages of the mutant neutrophil elastase (NE) encoded by <jats:italic>ELANE<\/jats:italic>. However, the enzyme affinity to the classic substrate Suc\u2013Ala\u2013Ala\u2013Ala\u2013pNA was not substantially changed, suggesting that the impaired integrity and stability of the mutant NE, rather than catalytic deficiency, might be the pathogenic mechanism of <jats:italic>ELANE<\/jats:italic> mutation-induced neutropenia. The patient was prescribed scaling and root planing (SRP) and monthly periodontal maintenance without systemic management. Although the routine periodontal treatment was occasionally interrupted by the 2019 coronavirus pandemic, her periodontal devastation remained well-remitted in the 5-year follow-up assessment. The results of this study confirmed the importance of plaque control and proper diagnosis in the periodontal management of such patients and provide better clinical references. In addition, the novel mutations identified in this study expand the spectrum of known <jats:italic>ELANE<\/jats:italic> mutations in CyN and further contribute to knowledge regarding its pathogenic mechanism.<\/jats:p>","DOI":"10.3389\/fgene.2022.972598","type":"journal-article","created":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T05:21:01Z","timestamp":1667280061000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Case report: Five-year periodontal management of a patient with two novel mutation sites in ELANE-induced cyclic neutropenia"],"prefix":"10.3389","volume":"13","author":[{"given":"Zhentao","family":"Lao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarun","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiying","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiwen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongheng","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoming","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingyu","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e17372","DOI":"10.1097\/MD.0000000000017372","article-title":"Management of tooth extraction in a patient with ELANE gene mutation-induced cyclic neutropenia: A case report","volume":"98","author":"Aota","year":"2019","journal-title":"Medicine"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1016\/j.joms.2015.03.073","article-title":"Full-arch rehabilitation of a patient with cyclic neutropenia","volume":"73","author":"Block","year":"2015","journal-title":"J. Oral Maxillofac. Surg."},{"key":"B3","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1182\/blood-2013-11-537068","article-title":"Severe congenital neutropenia: New lane for ELANE","volume":"123","author":"Borregaard","year":"2014","journal-title":"Blood"},{"key":"B4","doi-asserted-by":"publisher","first-page":"452","DOI":"10.3346\/jkms.2014.29.3.452","article-title":"Different clinical phenotypes in familial severe congenital neutropenia cases with same mutation of the ELANE gene","volume":"29","author":"Cho","year":"2014","journal-title":"J. Korean Med. Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1111\/j.1754-4505.2000.tb00017.x","article-title":"Early tooth loss due to cyclic neutropenia: Long-term follow-up of one patient","volume":"20","author":"da Fonseca","year":"2000","journal-title":"Special Care Dent."},{"key":"B6","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/0268-960X(88)90023-9","article-title":"Cyclic neutropenia: A clinical review","volume":"2","author":"Dale","year":"1988","journal-title":"Blood Rev."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2317","DOI":"10.1182\/blood.V96.7.2317","article-title":"Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia","volume":"96","author":"Dale","year":"2000","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1002\/humu.22308","article-title":"The spectrum of ELANE mutations and their implications in severe congenital and cyclic neutropenia","volume":"34","author":"Germeshausen","year":"2013","journal-title":"Hum. Mutat."},{"key":"B9","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1046\/j.1365-2141.2001.03069.x","article-title":"Mutations in the gene encoding neutrophil elastase (ELA2) are not sufficient to cause the phenotype of congenital neutropenia","volume":"115","author":"Germeshausen","year":"2001","journal-title":"Br. J. Haematol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1001\/archderm.1960.01580030038004","article-title":"The oral manifestations of cyclic (periodic) neutropenia. Does periadenitis mucosa necrotica recurrens (sutton) exist? A need for reevaluation","volume":"82","author":"Gorlin","year":"1960","journal-title":"Arch. Dermatol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1902\/jop.2000.71.9.1499","article-title":"The relationship between peripheral levels of leukocytes and neutrophils and periodontal disease status in a patient with congenital neutropenia","volume":"71","author":"Goultschin","year":"2000","journal-title":"J. Periodontol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1111\/j.1834-7819.1998.tb00144.x","article-title":"A case of chronic severe neutropenia: Oral findings and consequences of short-term granulocyte colony-stimulating factor treatment","volume":"43","author":"Hast\u00fcrk","year":"1998","journal-title":"Aust. Dent. J."},{"key":"B13","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1038\/70544","article-title":"Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis","volume":"23","author":"Horwitz","year":"1999","journal-title":"Nat. Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.hoc.2012.10.004","article-title":"ELANE mutations in cyclic and severe congenital neutropenia\u2014genetics and pathophysiology","volume":"27","author":"Horwitz","year":"2013","journal-title":"Hematol. Oncol. Clin. North Am."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.1182\/blood-2006-08-019166","article-title":"Neutrophil elastase in cyclic and severe congenital neutropenia","volume":"109","author":"Horwitz","year":"2007","journal-title":"Blood"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.1038\/s41598-020-58585-4","article-title":"Analysis of endothelin-1 concentrations in individuals with periodontitis","volume":"10","author":"Isola","year":"2020","journal-title":"Sci. Rep."},{"key":"B17","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1136\/jcp.54.1.7","article-title":"Neutrophil disorders and their management","volume":"54","author":"Lakshman","year":"2001","journal-title":"J. Clin. Pathol."},{"key":"B18","first-page":"159","article-title":"Severe periodontitis in a patient with cyclic neutropenia: A case report of long-term follow-up","volume":"15","author":"Lu","year":"2012","journal-title":"Chin. J. Dent. Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1097\/MOH.0000000000000105","article-title":"The diversity of mutations and clinical outcomes for ELANE-associated neutropenia","volume":"22","author":"Makaryan","year":"2015","journal-title":"Curr. Opin. Hematol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1111\/nyas.14309","article-title":"New insights into the pathomechanism of cyclic neutropenia","volume":"1466","author":"Mir","year":"2020","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"3539","DOI":"10.1182\/blood-2010-10-311704","article-title":"Activation of the unfolded protein response is associated with impaired granulopoiesis in transgenic mice expressing mutant Elane","volume":"117","author":"Nanua","year":"2011","journal-title":"Blood"},{"key":"B22","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1002\/pbc.22537","article-title":"Cyclic neutropenia and severe congenital neutropenia in patients with a shared ELANE mutation and paternal haplotype: Evidence for phenotype determination by modifying genes","volume":"55","author":"Newburger","year":"2010","journal-title":"Pediatr. Blood Cancer"},{"key":"B23","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1902\/jop.1996.67.4.454","article-title":"The importance of regular dental treatment in patients with cyclic neutropenia. Follow-up of 2 cases","volume":"67","author":"Pernu","year":"1996","journal-title":"J. Periodontol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1159\/000247542","article-title":"Cyclic neutropenia: A cause of recurrent aphthous stomatitis not to be missed","volume":"184","author":"R\u00f3denas","year":"1992","journal-title":"Dermatol. (Basel, Switz."},{"key":"B25","doi-asserted-by":"publisher","first-page":"653932","DOI":"10.3389\/fimmu.2021.653932","article-title":"Neutrophil elastase defects in congenital neutropenia","volume":"12","author":"Rydzynska","year":"2021","journal-title":"Front. Immunol."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp054630","article-title":"Clinical practice. Aphthous ulceration","volume":"355","author":"Scully","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"17032","DOI":"10.1038\/nrdp.2017.32","article-title":"Severe congenital neutropenias","volume":"3","author":"Skokowa","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1126\/science.1209038","article-title":"The unfolded protein response: From stress pathway to homeostatic regulation","volume":"334","author":"Walter","year":"2011","journal-title":"Sci. (New York, N.Y.)"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/00005792-198101000-00001","article-title":"Human cyclic neutropenia: Clinical review and long-term follow-up of patients","volume":"60","author":"Wright","year":"1981","journal-title":"Med. Baltim."},{"key":"B30","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1111\/j.1365-2141.2009.07888.x","article-title":"Prevalence of mutations in ELANE, GFI1, HAX1, SBDS, WAS and G6PC3 in patients with severe congenital neutropenia","volume":"147","author":"Xia","year":"2009","journal-title":"Br. J. Haematol."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.972598\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T05:21:07Z","timestamp":1667280067000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.972598\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,1]]},"references-count":30,"alternative-id":["10.3389\/fgene.2022.972598"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.972598","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,1]]},"article-number":"972598"}}