{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:46:55Z","timestamp":1791841615860,"version":"4.3.4"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009043","name":"University of Patras","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009043","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Obesity Pillars"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1016\/j.obpill.2026.100330","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T16:06:28Z","timestamp":1788365188000},"page":"100330","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Genetic variants of the leptin\u2013melanocortin pathway in a clinically selected Greek cohort with severe early-onset obesity and hyperphagia: implications for precision obesity medicine"],"prefix":"10.1016","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7051-7537","authenticated-orcid":false,"given":"Eirini","family":"Kostopoulou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diamantina X.","family":"Spilioti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos D.","family":"Pantzaris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Kehagias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7691-6355","authenticated-orcid":false,"given":"Dimitrios","family":"Kehagias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Markantes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4095-6827","authenticated-orcid":false,"given":"Eleni","family":"Papachatzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neoklis","family":"Georgopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bessie E.","family":"Spiliotis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"10","key":"10.1016\/j.obpill.2026.100330_bib1","doi-asserted-by":"crossref","first-page":"787","DOI":"10.3390\/cimb47100787","article-title":"Obesity as a multifactorial chronic disease: molecular mechanisms, systemic impact, and emerging digital interventions","volume":"47","author":"M\u0142ynarska","year":"2025","journal-title":"Curr Issues Mol Biol"},{"key":"10.1016\/j.obpill.2026.100330_bib2","doi-asserted-by":"crossref","DOI":"10.3389\/fped.2020.581461","article-title":"Childhood and adolescent obesity: a review","volume":"8","author":"Kansra","year":"2021","journal-title":"Front Pediatr"},{"key":"10.1016\/j.obpill.2026.100330_bib3","article-title":"Differentiating monogenic and syndromic obesities from polygenic obesity: assessment, diagnosis, and management","volume":"11","author":"Fitch","year":"2024","journal-title":"Obesity Pill"},{"issue":"4","key":"10.1016\/j.obpill.2026.100330_bib4","doi-asserted-by":"crossref","first-page":"226","DOI":"10.23838\/pfm.2022.00156","article-title":"The genetics of obesity A narrative review","volume":"6","author":"Sohn","year":"2022","journal-title":"Precis Future Med"},{"issue":"7","key":"10.1016\/j.obpill.2026.100330_bib5","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1038\/oby.2007.216","article-title":"Assessment of hyperphagia in Prader-Willi syndrome","volume":"15","author":"Dykens","year":"2007","journal-title":"Obesity (Silver Spring)"},{"issue":"5","key":"10.1016\/j.obpill.2026.100330_bib6","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"issue":"11","key":"10.1016\/j.obpill.2026.100330_bib7","doi-asserted-by":"crossref","first-page":"e3774","DOI":"10.1210\/clinem\/dgaf132","article-title":"Effects of rare coding variants in severe early-onset obesity genes in the population-based UK Biobank study","volume":"110","author":"Jia","year":"2025","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.obpill.2026.100330_bib8","doi-asserted-by":"crossref","DOI":"10.1016\/j.molmet.2021.101206","article-title":"The melanocortin pathway and energy homeostasis: from discovery to obesity therapy","volume":"48","author":"Yeo","year":"2021","journal-title":"Mol Metabol"},{"issue":"8","key":"10.1016\/j.obpill.2026.100330_bib9","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aat0866","article-title":"Regulation of energy rheostasis by the melanocortin-3 receptor","volume":"4","author":"Ghamari-Langroudi","year":"2018","journal-title":"Sci Adv"},{"issue":"1","key":"10.1016\/j.obpill.2026.100330_bib10","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ymgme.2017.03.007","article-title":"Next-generation sequencing of the monogenic obesity genes LEP, LEPR, MC4R, PCSK1 and POMC in a Norwegian cohort of patients with morbid obesity and normal weight controls","volume":"121","author":"Nordang","year":"2017","journal-title":"Mol Genet Metabol"},{"key":"10.1016\/j.obpill.2026.100330_bib11","first-page":"117","article-title":"Bardet-Biedl Syndrome overview","author":"Forsyth","year":"2023","journal-title":"Genet Genom Eye Disease: Adv Precis Med"},{"issue":"11","key":"10.1016\/j.obpill.2026.100330_bib12","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1038\/s41431-024-01634-7","article-title":"Bardet-Biedl syndrome improved diagnosis criteria and management: Inter European Reference Networks consensus statement and recommendations","volume":"32","author":"Dollfus","year":"2024","journal-title":"Eur J Hum Genet"},{"key":"10.1016\/j.obpill.2026.100330_bib13","doi-asserted-by":"crossref","DOI":"10.3389\/fped.2021.652011","article-title":"Identification of a rare Exon 19 skipping mutation in ALMS1 gene in alstr\u00f6m syndrome patients from two unrelated saudi families","volume":"9","author":"Saadah","year":"2021","journal-title":"Front Pediatr"},{"key":"10.1016\/j.obpill.2026.100330_bib14","article-title":"Unraveling Alstr\u00f6m syndrome: homozygous mutation c.2729C>G in ALMS1 gene across an extended family","volume":"12","author":"Abosabie","year":"2024","journal-title":"Mol Genet Genom Med"},{"issue":"1","key":"10.1016\/j.obpill.2026.100330_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.mcpro.2023.100701","article-title":"Interactome analysis reveals a link of the novel ALMS1-CEP70 complex to centrosomal clusters","volume":"23","author":"Woerz","year":"2024","journal-title":"Mol Cell Proteomics"},{"issue":"10","key":"10.1016\/j.obpill.2026.100330_bib16","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1002\/ajmg.a.62380","article-title":"Possible underreporting of pathogenic variants in RAI1 causing Smith\u2013Magenis syndrome","volume":"185","author":"Boot","year":"2021","journal-title":"Am J Med Genet A"},{"issue":"4","key":"10.1016\/j.obpill.2026.100330_bib17","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/ng1126","article-title":"Mutations in RAI1 associated with Smith-Magenis syndrome","volume":"33","author":"Slager","year":"2003","journal-title":"Nat Genet"},{"key":"10.1016\/j.obpill.2026.100330_bib18","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.90333","article-title":"Smith-Magenis syndrome protein RAI1 regulates body weight homeostasis through hypothalamic BDNF-producing neurons and neurotrophin downstream signalling","volume":"12","author":"Javed","year":"2023","journal-title":"eLife"},{"issue":"2","key":"10.1016\/j.obpill.2026.100330_bib19","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.molmet.2016.12.004","article-title":"Kinase Suppressor of Ras 2 (KSR2) expression in the brain regulates energy balance and glucose homeostasis","volume":"6","author":"Guo","year":"2016","journal-title":"Mol Metabol"},{"issue":"8","key":"10.1016\/j.obpill.2026.100330_bib20","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1038\/s41366-022-01139-7","article-title":"Testing for rare genetic causes of obesity: findings and experiences from a pediatric weight management program","volume":"46","author":"Roberts","year":"2022","journal-title":"Int J Obes (Lond)"},{"issue":"4","key":"10.1016\/j.obpill.2026.100330_bib21","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.cell.2013.09.058","article-title":"KSR2 mutations are associated with obesity, insulin resistance, and impaired cellular fuel oxidation","volume":"155","author":"Pearce","year":"2013","journal-title":"Cell"},{"issue":"6","key":"10.1016\/j.obpill.2026.100330_bib22","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1086\/518047","article-title":"RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity","volume":"80","author":"Jenkins","year":"2007","journal-title":"Am J Hum Genet"},{"issue":"1","key":"10.1016\/j.obpill.2026.100330_bib23","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1242\/dev.02169","article-title":"Signaling from Smo to Ci\/Gli: conservation and divergence of Hedgehog pathways from Drosophila to vertebrates","volume":"133","author":"Huangfu","year":"2006","journal-title":"Development"},{"key":"10.1016\/j.obpill.2026.100330_bib24","doi-asserted-by":"crossref","DOI":"10.1038\/boneres.2017.44","article-title":"AFF1 and AFF4 differentially regulate the osteogenic differentiation of human MSCs","volume":"5","author":"Zhou","year":"2017","journal-title":"Bone Res"},{"issue":"5","key":"10.1016\/j.obpill.2026.100330_bib25","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/s41574-021-00471-8","article-title":"Lipid and glucose metabolism in white adipocytes: pathways, dysfunction and therapeutics","volume":"17","author":"Morigny","year":"2021","journal-title":"Nat Rev Endocrinol"},{"issue":"9","key":"10.1016\/j.obpill.2026.100330_bib26","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1010425","article-title":"AFF4 regulates cellular adipogenic differentiation via targeting autophagy","volume":"18","author":"Chen","year":"2022","journal-title":"PLoS Genet"},{"issue":"1","key":"10.1016\/j.obpill.2026.100330_bib27","article-title":"Steroid receptor coactivator-1 modulates the function of Pomc neurons and energy homeostasis","volume":"10","author":"Yang","year":"2019","journal-title":"Nat Commun"},{"issue":"6","key":"10.1016\/j.obpill.2026.100330_bib28","doi-asserted-by":"crossref","first-page":"e2532","DOI":"10.1210\/clinem\/dgac067","article-title":"Obesity due to steroid receptor Coactivator-1 deficiency is associated with endocrine and metabolic abnormalities","volume":"107","author":"Cacciottolo","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"issue":"7","key":"10.1016\/j.obpill.2026.100330_bib29","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1093\/emboj\/18.7.1900","article-title":"Mice deficient in the steroid receptor co-activator 1 (SRC-1) are resistant to thyroid hormone","volume":"18","author":"Weiss","year":"1999","journal-title":"EMBO J"},{"key":"10.1016\/j.obpill.2026.100330_bib30","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2021.694204","article-title":"Central 5-HTR2C in the control of metabolic homeostasis","volume":"12","author":"Yao","year":"2021","journal-title":"Front Endocrinol"},{"issue":"12","key":"10.1016\/j.obpill.2026.100330_bib31","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1038\/s41591-022-02106-5","article-title":"Human loss-of-function variants in the serotonin 2C receptor associated with obesity and maladaptive behavior","volume":"28","author":"He","year":"2022","journal-title":"Nat Med"},{"key":"10.1016\/j.obpill.2026.100330_bib32","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1146\/annurev.ph.50.030188.001521","article-title":"Carboxypeptidase E","volume":"50","author":"Fricker","year":"1988","journal-title":"Annu Rev Physiol"},{"issue":"4","key":"10.1016\/j.obpill.2026.100330_bib33","doi-asserted-by":"crossref","first-page":"R18","DOI":"10.1530\/EC-17-0020","article-title":"Dissecting carboxypeptidase E: properties, functions and pathophysiological roles in disease","volume":"6","author":"Ji","year":"2017","journal-title":"Endocr Connect"},{"issue":"4","key":"10.1016\/j.obpill.2026.100330_bib34","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1210\/en.2003-1442","article-title":"Deficits in reproduction and pro-gonadotropin-releasing hormone processing in Male cpefat mice","volume":"145","author":"Srinivasan","year":"2004","journal-title":"Endocrinology"},{"issue":"1","key":"10.1016\/j.obpill.2026.100330_bib35","doi-asserted-by":"crossref","first-page":"52","DOI":"10.4274\/jcrpe.galenos.2020.2020.0101","article-title":"A new cause of obesity syndrome associated with a mutation in the carboxypeptidase gene detected in three siblings with obesity, intellectual disability and hypogonadotropic hypogonadism","volume":"13","author":"Durmaz","year":"2021","journal-title":"J Clin Res Pediatr Endocrinol"},{"key":"10.1016\/j.obpill.2026.100330_bib36","article-title":"New features in a rare monogenic obesity: carboxypeptidase E deficiency","author":"Emet","year":"2025","journal-title":"Horm Res Paediatr"},{"issue":"1","key":"10.1016\/j.obpill.2026.100330_bib37","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.tem.2006.11.007","article-title":"SH2B1 (SH2-B) and JAK2: a multifunctional adaptor protein and kinase made for each other","volume":"18","author":"Maures","year":"2007","journal-title":"Trends Endocrinol Metab"},{"issue":"11","key":"10.1016\/j.obpill.2026.100330_bib38","doi-asserted-by":"crossref","first-page":"6633","DOI":"10.1128\/MCB.17.11.6633","article-title":"Identification of SH2-Bbeta as a substrate of the tyrosine kinase JAK2 involved in growth hormone signaling","volume":"17","author":"Rui","year":"1997","journal-title":"Mol Cell Biol"},{"issue":"31","key":"10.1016\/j.obpill.2026.100330_bib39","article-title":"SH2B1 defends against energy imbalance, obesity, and metabolic disease via a paraventricular hypothalamus\u2192dorsal raphe nucleus neurocircuit","volume":"11","author":"Li","year":"2024","journal-title":"Adv Sci (Weinh)"},{"key":"10.1016\/j.obpill.2026.100330_bib40","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2019.109651","article-title":"New perspective on SH2B1: an accelerator of cancer progression","volume":"121","author":"Cheng","year":"2020","journal-title":"Biomed Pharmacother"},{"issue":"1","key":"10.1016\/j.obpill.2026.100330_bib41","first-page":"1","article-title":"Severe early onset obesity and hypopituitarism in a child with a novel SIM1 gene mutation","volume":"2020","author":"Gonsalves","year":"2020","journal-title":"Endocrinol Diabetes Metab Case Rep"},{"issue":"7","key":"10.1016\/j.obpill.2026.100330_bib42","doi-asserted-by":"crossref","first-page":"3037","DOI":"10.1172\/JCI68035","article-title":"Loss-of-function mutations in SIM1 contribute to obesity and prader-willi\u2013like features","volume":"123","author":"Bonnefond","year":"2013","journal-title":"J Clin Investig"},{"issue":"10","key":"10.1016\/j.obpill.2026.100330_bib43","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s11892-018-1053-x","article-title":"Genetics of severe obesity","volume":"18","author":"Fairbrother","year":"2018","journal-title":"Curr Diabetes Rep"},{"key":"10.1016\/j.obpill.2026.100330_bib44","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s40246-025-00895-7","article-title":"Severe obesity as an oligogenic condition: evidence from 1714 adults seeking treatment in the UK National Health Service","volume":"20","author":"Almansoori","year":"2025","journal-title":"Hum Genom"},{"issue":"3","key":"10.1016\/j.obpill.2026.100330_bib45","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1210\/jc.2016-2573","article-title":"Pediatric Obesity\u2014Assessment, treatment, and prevention: an Endocrine Society Clinical Practice Guideline","volume":"102","author":"Styne","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.obpill.2026.100330_bib46","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1038\/s41366-022-01139-7","article-title":"Testing for rare genetic causes of obesity: findings and experiences from a pediatric weight management program","volume":"46","author":"Roberts","year":"2022","journal-title":"Int J Obes (Lond)"},{"key":"10.1016\/j.obpill.2026.100330_bib47","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1038\/s41366-025-01819-0","article-title":"Detecting monogenic obesity: a systematic exome-wide workup of over 500 individuals","volume":"49","author":"Kunzel","year":"2025","journal-title":"Int J Obes"},{"key":"10.1016\/j.obpill.2026.100330_bib48","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1056\/NEJMoa1512693","article-title":"Proopiomelanocortin deficiency treated with a Melanocortin-4 receptor agonist","volume":"375","author":"K\u00fchnen","year":"2016","journal-title":"N Engl J Med"},{"issue":"7","key":"10.1016\/j.obpill.2026.100330_bib49","doi-asserted-by":"crossref","DOI":"10.1016\/j.gim.2026.102583","article-title":"Points to consider for the reporting of variants of uncertain significance in germline genetic and genomic testing: a statement of the American College of Medical Genetics and Genomics (ACMG)","volume":"28","author":"Mighton","year":"2026","journal-title":"Genet Med"}],"container-title":["Obesity Pillars"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2667368126000860?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2667368126000860?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:08:54Z","timestamp":1791839334000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2667368126000860"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,12]]},"references-count":49,"alternative-id":["S2667368126000860"],"URL":"https:\/\/doi.org\/10.1016\/j.obpill.2026.100330","relation":{},"ISSN":["2667-3681"],"issn-type":[{"value":"2667-3681","type":"print"}],"subject":[],"published":{"date-parts":[[2026,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Genetic variants of the leptin\u2013melanocortin pathway in a clinically selected Greek cohort with severe early-onset obesity and hyperphagia: implications for precision obesity medicine","name":"articletitle","label":"Article Title"},{"value":"Obesity Pillars","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.obpill.2026.100330","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Inc. on behalf of Obesity Medicine Association.","name":"copyright","label":"Copyright"}],"article-number":"100330"}}