{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T23:37:49Z","timestamp":1773617869841,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T00:00:00Z","timestamp":1672358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Generalized pustular psoriasis (GPP) is a rare form of psoriasis, which is characterized by sudden onset of repeated erythema and pustule formation with generalized inflammation. Recent advances in molecular genetics have led to the identification of several genes associated with GPP, including <jats:italic>IL36RN<\/jats:italic>, <jats:italic>CARD14<\/jats:italic>, <jats:italic>AP1S3<\/jats:italic>, <jats:italic>SERPINA3<\/jats:italic>, and <jats:italic>MPO<\/jats:italic>. Of these, only limited cases of GPP have been reported to carry mutations in the <jats:italic>AP1S3<\/jats:italic>, <jats:italic>SERPINA3<\/jats:italic>, or <jats:italic>MPO<\/jats:italic> to date. In the present study, we investigated a Japanese patient with GPP and found a homozygous missense mutation c.1769G&gt;T (p.Arg590Leu) in the <jats:italic>MPO<\/jats:italic> gene. Structural analysis predicted that the mutant MPO protein would abolish its ability to bind with heme protein. In vitro studies using cultured cells revealed that the mutant MPO was stably expressed, but completely lost its myeloperoxidase activity. Immunohistochemistry (IHC) using an anti\u2010MPO antibody showed markedly reduced expression of MPO protein in the patient's skin, suggesting that the mutation would lead to an instability of the MPO protein in vivo. Finally, IHC with an anti\u2010citrullinated Histone H3 antibody demonstrated a sparse formation of neutrophil extracellular traps within a Kogoj's spongiform pustule of the patient's skin. Collectively, we conclude that the c.1769G&gt;T (p.Arg590Leu) in the <jats:italic>MPO<\/jats:italic> is a complete loss\u2010of\u2010function mutation associated with GPP in the patient. Our data further underscore critical roles of the <jats:italic>MPO<\/jats:italic> gene in the pathogenesis of GPP.<\/jats:p>","DOI":"10.1111\/1346-8138.16700","type":"journal-article","created":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T03:50:30Z","timestamp":1672458630000},"page":"664-671","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A homozygous loss\u2010of\u2010function variant in the <i>MPO<\/i> gene is associated with generalized pustular psoriasis"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1485-1941","authenticated-orcid":false,"given":"Mami","family":"Onitsuka","sequence":"first","affiliation":[{"name":"Department of Dermatology Yamaguchi University Graduate School of Medicine  Ube Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Farooq","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Biotechnology Government College University Faisalabad (GCUF)  Faisalabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Nasir","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Institute of Biochemistry, Biotechnology and Bioinformatics (IBBB) The Islamia University of Bahawalpur  Bahawalpur Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuichiro","family":"Yasuno","sequence":"additional","affiliation":[{"name":"Department of Dermatology Yamaguchi University Graduate School of Medicine  Ube Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9727-8073","authenticated-orcid":false,"given":"Yutaka","family":"Shimomura","sequence":"additional","affiliation":[{"name":"Department of Dermatology Yamaguchi University Graduate School of Medicine  Ube 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