{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T22:42:56Z","timestamp":1784241776832,"version":"3.55.0"},"reference-count":23,"publisher":"The Endocrine Society","issue":"9","license":[{"start":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T00:00:00Z","timestamp":1655942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Elisabeth Foundation"},{"name":"Netherlands Organization of Scientific Research"},{"name":"ZonMW Vidi","award":["91716453"],"award-info":[{"award-number":["91716453"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Patients with pro-opiomelanocortin (POMC) defects generally present with early-onset obesity, hyperphagia, hypopigmentation and adrenocorticotropin (ACTH) deficiency. Rodent models suggest that adequate cleavage of ACTH to \u03b1-melanocortin\u2013stimulating hormone (\u03b1-MSH) and desacetyl-\u03b1-melanocortin\u2013stimulating hormone (d-\u03b1-MSH) by prohormone convertase 2 at the KKRR region is required for regulating food intake and energy balance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We present 2 sisters with a novel POMC gene variant, leading to an ACTH defect at the prohormone convertase 2 cleavage site, and performed functional studies of this variant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The patients had obesity, hyperphagia and hypocortisolism, with markerly raised levels of ACTH but unaffected pigmentation. Their ACTH has reduced potency to stimulate the melanocortin (MC) 2 receptor, explaining their hypocortisolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The hyperphagia and obesity support evidence that adequate cleavage of ACTH to \u03b1-MSH and d-\u03b1-MSH is also required in humans for feeding control.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgac342","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T13:09:53Z","timestamp":1655989793000},"page":"e3699-e3704","source":"Crossref","is-referenced-by-count":15,"title":["Obesity and Hyperphagia With Increased Defective ACTH: A Novel\n                    <i>POMC<\/i>\n                    Variant"],"prefix":"10.1210","volume":"107","author":[{"given":"Eline S","family":"van der Valk","sequence":"first","affiliation":[{"name":"Obesity Centre CGG, Erasmus University Medical Center Rotterdam , 3000 CA Rotterdam , the Netherlands"},{"name":"Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center Rotterdam , 3000 CA Rotterdam , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotte","family":"Kleinendorst","sequence":"additional","affiliation":[{"name":"Obesity Centre CGG, Erasmus University Medical Center Rotterdam , 3000 CA Rotterdam , the Netherlands"},{"name":"Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam , 1100 DD Amsterdam , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patric J D","family":"Delhanty","sequence":"additional","affiliation":[{"name":"Obesity Centre CGG, Erasmus University Medical Center Rotterdam , 3000 CA Rotterdam , the Netherlands"},{"name":"Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center Rotterdam , 3000 CA Rotterdam , the 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Haelst","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam , 1100 DD Amsterdam , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura C G","family":"de Graaff","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center Rotterdam , 3000 CA Rotterdam , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Huisman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center Rotterdam , 3000 CA Rotterdam , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"White","sequence":"additional","affiliation":[{"name":"Divison of Diabetes, Endocrinology & Gastroenterology, Faculty of Biology, Medicine and Health, University of Manchester , 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