{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:50:40Z","timestamp":1787028640456,"version":"build-2736575974"},"reference-count":43,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T00:00:00Z","timestamp":1696636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Rhythm Pharmaceuticals Inc. (Boston, USA)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: The genetic contribution to obesity is substantial and may underpin the altered pathophysiology. One such pathway involves melanocortin signaling in the hypothalamus. Genetic variants can cause dysregulation in the central melanocortin pathway that can result in early onset of hyperphagia and obesity. Clinically identifying patients who are at risk of known genetic mutations is challenging. The main purpose of this study was to identify associations between the clinico-demographical characteristics and the presence of a genetic mutation associated with obesity. Methods: We tested samples from 238 adult patients with class III obesity between October 2021 to February 2023 using next-generation sequencing (NGS) (Illumina, NovaSeq 6000 Sequencing System). The results were classified as \u201cno variant identified\u201d or \u201cvariant identified\u201d. Results: 107 patients (45%) had one or more gene mutation in the leptin\u2013melanocortin pathway. All variants were heterozygous. The patients with a gene mutation had a BMI of 48.4 \u00b1 0.8 kg\/m2 (mean \u00b1 SEM), and those without a gene mutation had a BMI of 49.4 \u00b1 0.7 kg\/m2 (p = 0.4). The mean age of onset of obesity in patients with a gene mutation was 13.9 \u00b1 1.3 years and for those without gene mutations was 11.5 \u00b1 0.9 years (p = 0.1). The incidence of hyperphagia as a child was also not predictive (p = 0.4). Conclusions: Gene mutations associated with obesity in patients with a BMI &gt; 40 kg\/m2 are common. However, a patient\u2019s BMI, age of onset of obesity, or age of onset of hyperphagia did not help to differentiate which patients may be more likely to have genetic mutations associated with obesity.<\/jats:p>","DOI":"10.3390\/jcm12196396","type":"journal-article","created":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T04:52:36Z","timestamp":1696827156000},"page":"6396","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Obesity Characteristics Are Poor Predictors of Genetic Mutations Associated with Obesity"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5250-8269","authenticated-orcid":false,"given":"Ahmed W.","family":"Al-Humadi","sequence":"first","affiliation":[{"name":"Diabetes Complications Research Centre, Conway Institute, University College Dublin, D04V1W8 Dublin, Ireland"},{"name":"Department of Dentistry, Hilla University College, Babylon 510001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6323-2525","authenticated-orcid":false,"given":"Khaled","family":"Alabduljabbar","sequence":"additional","affiliation":[{"name":"Diabetes Complications Research Centre, Conway Institute, University College Dublin, D04V1W8 Dublin, Ireland"},{"name":"Department of Family Medicine and Polyclinics, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5234-5797","authenticated-orcid":false,"given":"Moath S.","family":"Alsaqaaby","sequence":"additional","affiliation":[{"name":"Diabetes Complications Research Centre, Conway Institute, University College Dublin, D04V1W8 Dublin, Ireland"},{"name":"Obesity, Endocrine and Metabolism Centre, King Fahad Medical City, Riyadh 11525, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hani","family":"Talaee","sequence":"additional","affiliation":[{"name":"Diabetes Complications Research Centre, Conway Institute, University College Dublin, D04V1W8 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5521-5445","authenticated-orcid":false,"given":"Carel W.","family":"le Roux","sequence":"additional","affiliation":[{"name":"Diabetes Complications Research Centre, Conway Institute, University College Dublin, D04V1W8 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1056\/NEJMoa1614362","article-title":"Health Effects of Overweight and Obesity in 195 Countries over 25 Years","volume":"377","author":"Afshin","year":"2017","journal-title":"N. 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