{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T06:29:30Z","timestamp":1759991370136,"version":"3.37.3"},"reference-count":10,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T00:00:00Z","timestamp":1539129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"JSPS KAKENHI"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>TGM1<\/jats:italic> is the most common gene responsible for lamellar ichthyosis. Previous studies have suggested that patients with lamellar ichthyosis carrying two missense mutations in <jats:italic>TGM1<\/jats:italic> show significantly less severe phenotypes than those with at least one truncating mutation in <jats:italic>TGM1<\/jats:italic>. Here, we report a patient with severe lamellar ichthyosis who was compound heterozygous for <jats:italic>TGM1<\/jats:italic> missense mutations, including a novel one. A 22\u2010year\u2010old Japanese man presented with large, dark brown, plate\u2010like scales on the extremities and small adherent scales on the face and trunk. His other clinical findings included ectropion, hair loss, hypohidrosis, hyperthermia in summer, palmoplantar keratoderma and constriction of the fingers. Dermoscopy revealed accentuated sulci cutis with numerous large keratotic plugs in the cristae cutis. Histologically, orthohyperkeratosis and mild acanthosis were noted. Electron microscopy showed reduced cornified envelope thickness and numerous lipid droplets in the stratum corneum. Mutation analysis revealed the patient to be compound heterozygous for missense mutations, c.620T&gt;C (p.Leu207Pro) and c.1631A&gt;G (p.Tyr544Cys), in <jats:italic>TGM1<\/jats:italic>. Furthermore, we showed that TGM1 enzymatic activity was largely absent in his epidermis. These findings led us to diagnose him as having lamellar ichthyosis. This study has two important notions. First, even two missense mutations in <jats:italic>TGM1<\/jats:italic> can cause severe lamellar ichthyosis. Second, this is the first report of dermoscopic findings of lamellar ichthyosis, implicating the obstruction of sweat glands by keratotic plugs in the pathogenesis of hypohidrosis in the disease. In conclusion, this study provides further insights into genotype\u2013phenotype correlations and pathogenesis in lamellar ichthyosis.<\/jats:p>","DOI":"10.1111\/1346-8138.14675","type":"journal-article","created":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T08:59:50Z","timestamp":1539161990000},"page":"1463-1467","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Compound heterozygous missense mutations p.Leu207Pro and p.Tyr544Cys in <i>TGM1<\/i> cause a severe form of lamellar ichthyosis"],"prefix":"10.1111","volume":"45","author":[{"given":"Masae","family":"Takeda","sequence":"first","affiliation":[{"name":"Department of Dermatology Hokkaido University Graduate School of Medicine Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9954-6446","authenticated-orcid":false,"given":"Toshifumi","family":"Nomura","sequence":"additional","affiliation":[{"name":"Department of Dermatology Hokkaido University Graduate School of Medicine Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takato","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Science Tohoku University Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshinari","family":"Miyauchi","sequence":"additional","affiliation":[{"name":"Department of Dermatology Hokkaido University Graduate School of Medicine Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shotaro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Dermatology Hokkaido University Graduate School of Medicine Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuyuki","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Dermatology Hokkaido University Graduate School of Medicine Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Dermatology Hokkaido University Graduate School of Medicine Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,10,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.13243"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.060905"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pedneo.2018.01.003"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20952"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.181008"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.4103\/0378-6323.154786"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0923-1811(00)00087-6"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/ced.12410"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.22.13693"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.1998.02024.x"}],"container-title":["The Journal of Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2F1346-8138.14675","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1346-8138.14675","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T02:19:11Z","timestamp":1694744351000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1346-8138.14675"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,10]]},"references-count":10,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["10.1111\/1346-8138.14675"],"URL":"https:\/\/doi.org\/10.1111\/1346-8138.14675","archive":["Portico"],"relation":{},"ISSN":["0385-2407","1346-8138"],"issn-type":[{"type":"print","value":"0385-2407"},{"type":"electronic","value":"1346-8138"}],"subject":[],"published":{"date-parts":[[2018,10,10]]},"assertion":[{"value":"2018-06-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}