{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T09:15:09Z","timestamp":1788340509230,"version":"build-2803163510"},"reference-count":18,"publisher":"Wiley","issue":"S2","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Setmelanotide, a melanocortin 4 receptor (MC4R) agonist, is a promising pharmacological treatment option for people with rare monogenic obesity conditions affecting the leptin\u2010melanocortin signaling pathway, including proprotein convertase subtilisin\/kexin type 1 (\n                    <jats:italic>PCSK1<\/jats:italic>\n                    ) gene mutations. It has been studied in people with homozygous mutations causing a complete deficiency of\n                    <jats:italic>PCSK1<\/jats:italic>\n                    . We report the first case of a 40\u2010year\u2010old female with a heterozygous\n                    <jats:italic>PCSK1<\/jats:italic>\n                    N221D (c.661 A&gt;G) variant mutation leading to severe early\u2010onset treatment\u2010resistant obesity with previous suboptimal response to bariatric surgery and conventional obesity medications, who achieved a total weight loss of 11.8% with setmelanotide treatment over the course of 3\u2009months. Although her mutation confers a loss of 10% to 30% enzymatic function in in\u00a0vitro studies, setmelanotide was highly effective in treating her obesity. It is also the first reported case of a cutaneous adverse effect of setmelanotide in the form of severe skin hyperpigmentation in a patient with a pathogenic\n                    <jats:italic>PCSK1<\/jats:italic>\n                    variant. This case underscores the effectiveness and safety of setmelanotide in a heterozygous\n                    <jats:italic>PCSK1<\/jats:italic>\n                    mutation.\n                  <\/jats:p>","DOI":"10.1002\/oby.70213","type":"journal-article","created":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T05:43:38Z","timestamp":1777700618000},"page":"70-74","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effectiveness and Safety of Setmelanotide in a Patient With a Heterozygous\n                    <scp>\n                      <i>PCSK1<\/i>\n                    <\/scp>\n                    Deficiency"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5651-9010","authenticated-orcid":false,"given":"Ellina","family":"Lytvyak","sequence":"first","affiliation":[{"name":"Department of Medicine University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6239-6663","authenticated-orcid":false,"given":"Arshdeep","family":"Rattol","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9332-7069","authenticated-orcid":false,"given":"Eduardo","family":"Grunvald","sequence":"additional","affiliation":[{"name":"School of Medicine University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes13101746"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018\u201001854"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.177"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv097"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/db11\u20100305"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014\u20104024"},{"issue":"1","key":"e_1_2_10_8_1","first-page":"17","article-title":"Treating Genetic Obesity With the Novel Agent Setmelanotide","volume":"49","author":"Gor P.","year":"2024","journal-title":"US Pharmacist"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010021\u201001470\u20109"},{"key":"e_1_2_10_10_1","unstructured":"IMCIVREE (Setmelanotide) Injection for Subcutaneous Use (Rhythm Pharmaceuticals 2020) accessed July 24 2025 https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/213793s000lbl.pdf."},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20108587(20)30364\u20108"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvac150.031"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2015\u20101117"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2015\u20101068"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2019\u201000418"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200318784"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvac057"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm13101460"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12121874"}],"container-title":["Obesity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/oby.70213","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/oby.70213","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/oby.70213","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:25:32Z","timestamp":1788337532000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/oby.70213"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,1]]},"references-count":18,"journal-issue":{"issue":"S2","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/oby.70213"],"URL":"https:\/\/doi.org\/10.1002\/oby.70213","archive":["Portico"],"relation":{},"ISSN":["1930-7381","1930-739X"],"issn-type":[{"value":"1930-7381","type":"print"},{"value":"1930-739X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,1]]},"assertion":[{"value":"2026-02-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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