{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T19:20:57Z","timestamp":1777404057236,"version":"3.51.4"},"reference-count":30,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002842","name":"Chiang Mai University","doi-asserted-by":"publisher","award":["TGCMU2566P011\/2566"],"award-info":[{"award-number":["TGCMU2566P011\/2566"]}],"id":[{"id":"10.13039\/501100002842","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002842","name":"Chiang Mai University","doi-asserted-by":"publisher","award":["64-123"],"award-info":[{"award-number":["64-123"]}],"id":[{"id":"10.13039\/501100002842","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002842","name":"Chiang Mai University","doi-asserted-by":"publisher","award":["001\/2565"],"award-info":[{"award-number":["001\/2565"]}],"id":[{"id":"10.13039\/501100002842","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Health System Research Institute","award":["TGCMU2566P011\/2566"],"award-info":[{"award-number":["TGCMU2566P011\/2566"]}]},{"name":"Health System Research Institute","award":["64-123"],"award-info":[{"award-number":["64-123"]}]},{"name":"Health System Research Institute","award":["001\/2565"],"award-info":[{"award-number":["001\/2565"]}]},{"name":"Chiang Mai University Faculty of Medicine Research Fund","award":["TGCMU2566P011\/2566"],"award-info":[{"award-number":["TGCMU2566P011\/2566"]}]},{"name":"Chiang Mai University Faculty of Medicine Research Fund","award":["64-123"],"award-info":[{"award-number":["64-123"]}]},{"name":"Chiang Mai University Faculty of Medicine Research Fund","award":["001\/2565"],"award-info":[{"award-number":["001\/2565"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Reactive pustular eruptions (RPEs) can manifest in a variety of conditions, including pustular psoriasis (PP) and adult-onset immunodeficiency syndrome due to anti-interferon-\u03b3 autoantibody (AOID). These RPEs can be attributed to different causes, one of which is genetic factors. However, the genetic basis for pustular skin diseases remains poorly understood. In our study, we conducted whole-exome sequencing on a cohort of 17 AOID patients with pustular reactions (AOID-PR) and 24 PP patients. We found that 76% and 58% of the AOID-PR and PP patients, respectively, carried rare genetic variations within the filaggrin (FLG) gene family. A total of 12 out of 21 SNPs on FLG had previously received clinical classifications, with only p.Ser2706Ter classified as pathogenic. In contrast, none of the FLG3 SNPs identified in this study had prior clinical classifications. Overall, these variations had not been previously documented in cases of pustular disorders, and two of them were entirely novel discoveries. Immunohistochemical analysis of skin biopsies revealed that FLG variants like p.Ser860Trp, p.Gly3903Ter, p.Gly2440Glu, and p.Glu2133Asp caused reductions in FLG levels similar to the pathogenic FLG p.Ser2706Ter. These results highlight rare FLG variants as potential novel genetic risk factors contributing to pustule formation in both AOID and PP.<\/jats:p>","DOI":"10.3390\/ijms25126466","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T06:47:30Z","timestamp":1718174850000},"page":"6466","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Rare Filaggrin Variants Are Associated with Pustular Skin Diseases in Asians"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0558-356X","authenticated-orcid":false,"given":"Luca","family":"Lo Piccolo","sequence":"first","affiliation":[{"name":"Centre of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7478-240X","authenticated-orcid":false,"given":"Wasinee","family":"Wongkummool","sequence":"additional","affiliation":[{"name":"Centre of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7420-5135","authenticated-orcid":false,"given":"Phatcharida","family":"Jantaree","sequence":"additional","affiliation":[{"name":"Centre of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5968-218X","authenticated-orcid":false,"given":"Teerada","family":"Daroontum","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suteeraporn","family":"Chaowattanapanit","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3417-6210","authenticated-orcid":false,"given":"Charoen","family":"Choonhakarn","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Warayuwadee","family":"Amornpinyo","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Internal Medicine, Khon Kaen Hospital, Ministry of Public Health, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1241-5954","authenticated-orcid":false,"given":"Romanee","family":"Chaiwarith","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1597-7290","authenticated-orcid":false,"given":"Salin","family":"Kiratikanon","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0256-9343","authenticated-orcid":false,"given":"Rujira","family":"Rujiwetpongstorn","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Napatra","family":"Tovanabutra","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siri","family":"Chiewchanvit","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8581-397X","authenticated-orcid":false,"given":"Chumpol","family":"Ngamphiw","sequence":"additional","affiliation":[{"name":"National Biobank of Thailand, National Center for Genetic Engineering and Biotechnology (BIOTEC), Pathum Thani 12120, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3543-8136","authenticated-orcid":false,"given":"Worrachet","family":"Intachai","sequence":"additional","affiliation":[{"name":"Center of Excellence in Medical Genetics Research, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9841-0881","authenticated-orcid":false,"given":"Piranit","family":"Kantaputra","sequence":"additional","affiliation":[{"name":"Center of Excellence in Medical Genetics Research, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6654-3409","authenticated-orcid":false,"given":"Mati","family":"Chuamanochan","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"742","DOI":"10.2340\/00015555-2959","article-title":"Skin Manifestations in Patients with Adult-onset Immunodeficiency due to Anti-interferon-gamma Autoantibody: A Relationship with Systemic Infections","volume":"98","author":"Jutivorakool","year":"2018","journal-title":"Acta Derm. 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