{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T03:28:54Z","timestamp":1778902134272,"version":"3.51.4"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T00:00:00Z","timestamp":1710460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373459"],"award-info":[{"award-number":["82373459"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373500"],"award-info":[{"award-number":["82373500"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Inherited hyperpigmented skin disorders comprise a group of entities with considerable clinical and genetic heterogenicity. The genetic basis of a majority of these disorders remains to be elucidated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>This study aimed to identify the underlying gene for an unclarified disorder of autosomal-dominant generalized skin hyperpigmentation with or without glomuvenous malformation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Whole-exome sequencing was performed in five unrelated families with autosomal-dominant generalized skin hyperpigmentation. Variants were confirmed using Sanger sequencing and a minigene assay was employed to evaluate the splicing alteration. Immunofluorescence and transmission electron microscopy (TEM) were used to determine the quantity of melanocytes and melanosomes in hyperpigmented skin lesions. GLMN knockdown by small interfering RNA assays was performed in human MNT-1 cells to examine melanin concentration and the underlying molecular mechanism.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified five variants in GLMN in five unrelated families, including c.995_996insAACA(p.Ser333Thrfs*11), c.632 + 4delA, c.1470_1473dup(p.Thr492fs*12), c.1319G &amp;gt; A(p.Trp440*) and c.1613_1614insTA(Thr540*). The minigene assay confirmed that the c.632 + 4delA mutant resulted in abolishment of the canonical donor splice site. Although the number of melanocytes remained unchanged in skin lesions, as demonstrated by immunofluorescent staining of tyrosinase and premelanosome protein, TEM revealed an increased number of melanosomes in the skin lesion of a patient. The GLMN knockdown MNT-1 cells demonstrated a higher melanin concentration, a higher proportion of stage III and IV melanosomes, upregulation of microphthalmia-associated transcription factor and tyrosinase, and downregulation of phosphorylated p70S6\u2005K vs. mock-transfected cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We found that loss-of-function variants in GLMN are associated with generalized skin hyperpigmentation with or without glomuvenous malformation. Our study implicates a potential role of glomulin in human skin melanogenesis, in addition to vascular morphogenesis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bjd\/ljae108","type":"journal-article","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T20:18:34Z","timestamp":1710533914000},"page":"107-116","source":"Crossref","is-referenced-by-count":3,"title":["Loss-of-function variants in <i>GLMN<\/i> are associated with generalized skin hyperpigmentation with or without glomuvenous malformation"],"prefix":"10.1093","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9891-6353","authenticated-orcid":false,"given":"Xingyuan","family":"Jiang","sequence":"first","affiliation":[{"name":"Dermatology Hospital, Southern Medical University , Guangzhou , China"},{"name":"Department of Dermatology, Peking University First Hospital, Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, National Clinical Research Center for Skin and Immune Diseases , Beijing , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Yang","sequence":"additional","affiliation":[{"name":"Dermatology Hospital, Southern Medical University , Guangzhou , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health , Beijing , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Liang","sequence":"additional","affiliation":[{"name":"Dermatology Hospital, Southern Medical University , Guangzhou , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1020-793X","authenticated-orcid":false,"given":"Zhuoqing","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Peking University First Hospital, Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, National Clinical Research Center for Skin and Immune Diseases , Beijing , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shimiao","family":"Huang","sequence":"additional","affiliation":[{"name":"Dermatology Hospital, Southern Medical University , Guangzhou , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zigang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health , Beijing , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2970-746X","authenticated-orcid":false,"given":"Bin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health , Beijing , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoping","family":"Pei","sequence":"additional","affiliation":[{"name":"Dermatology Hospital, Southern Medical University , Guangzhou , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liangqi","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Xiamen University , Xiamen , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5414-1472","authenticated-orcid":false,"given":"Huijun","family":"Wang","sequence":"additional","affiliation":[{"name":"Dermatology Hospital, Southern Medical University , Guangzhou , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3240-1998","authenticated-orcid":false,"given":"Zhimiao","family":"Lin","sequence":"additional","affiliation":[{"name":"Dermatology Hospital, Southern Medical University , Guangzhou , China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,3,15]]},"reference":[{"key":"2024062015120128200_ljae108-B1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.jaad.2022.01.051","article-title":"Disorders of hyperpigmentation. 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