{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T07:28:13Z","timestamp":1775806093240,"version":"3.50.1"},"reference-count":10,"publisher":"Bioscientifica","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,8,1]]},"abstract":"<jats:sec>\n<jats:title>Summary<\/jats:title>\n<jats:p>Leptin is secreted by adipocytes in response to fat storage and binds to its receptor (LEPR), which is ubiquitously expressed throughout the body. Leptin regulates energy expenditure and is anorexigenic. In this study, we describe the clinical and hormonal findings of three siblings with a personal history of rapid weight gain during the first months of life. They had delayed puberty, high levels of FSH (15.6 \u00b1 3.7 mUI\/mL; reference: 1.5\u201312.4) and LH (12.3 \u00b1 2.2 mUI\/mL; reference: 1.7\u20138.6), normal oestradiol and total testosterone and successful fertility. None of the patients had dyslipidemia, diabetes or thyroid disease. Next-generation sequencing identified a pathogenic homozygous variant c.2357T&gt;C, p.(Leu786Pro) in <jats:italic>LEPR<\/jats:italic>. Their parents and children were heterozygous for this mutation. We compared clinical and biochemical findings of homozygous carriers with first-degree heterozygous family members and ten randomly selected patients with adult-onset morbid obesity. Homozygous carriers of the mutation had significantly higher BMI (32.2 \u00b1 1.7 kg\/m<jats:sup>2<\/jats:sup> vs 44.5 \u00b1 7.1 kg\/m<jats:sup>2<\/jats:sup>, <jats:italic>P<\/jats:italic>\u2009=\u20090.023) and increased serum levels of leptin (26.3 \u00b1 9.3 ng\/mL vs 80 \u00b1 36.4 ng\/mL, <jats:italic>P<\/jats:italic>\u2009=\u20090.028) than their heterozygous relatives. Compared with the ten patients with adult-onset morbid obesity, serum levels of leptin were not significantly higher in homozygous carriers (53.8 \u00b1 24.1 ng\/mL vs 80 \u00b1 36.4 ng\/mL, <jats:italic>P<\/jats:italic>\u2009=\u20090.149), and thus serum levels of leptin were not a useful discriminative marker of <jats:italic>LEPR<\/jats:italic> mutations. We described a rare three-generation family with monogenic obesity due to a mutation in<jats:italic> LEPR<\/jats:italic>. Patients with early onset obesity should be considered for genetic screening, as the identification of mutations may allow personalized treatment options (e.g. MC4R-agonists) and targeted successful weight loss.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Learning points<\/jats:title>\n<jats:list list-type=\"bullet\">\n<jats:list-item>\n<jats:p>The early diagnosis of monogenic forms of obesity can be of great interest since new treatments for these conditions are becoming available.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Since BMI and leptin levels in patients with leptin receptor mutations are not significantly different from those found in randomly selected morbid obese patients, a careful medical history is mandatory to suspect this condition.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Loss of leptin receptor function has been associated with infertility. However, our patients were able to conceive, emphasizing the need for genetic counselling in affected patients with this condition.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list>\n<\/jats:sec>","DOI":"10.1530\/edm-21-0124","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T14:03:27Z","timestamp":1661349807000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":11,"title":["Early onset obesity due to a mutation in the human leptin receptor gene"],"prefix":"10.1530","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6566-3209","authenticated-orcid":true,"given":"Carolina","family":"Chaves","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Nutrition, Hospital Divino Esp\u00edrito Santo de Ponta Delgada, EPER, Azores Islands, Portugal"}]},{"given":"Teresa","family":"Kay","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Hospital Dona Estef\u00e2nia, Centro Hospitalar de Lisboa Central, EPE, Lisbon, Portugal"}]},{"given":"Jo\u00e3o","family":"Anselmo","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Hospital Divino Esp\u00edrito Santo de Ponta Delgada, EPER, Azores Islands, Portugal"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Frontiers of Medicine","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s11684-013-0263-5","article-title":"Leptin signaling and leptin resistance","volume":"7","author":"Zhou","year":"2013","unstructured":"Zhou YRui L. 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