دورية أكاديمية
Rare antagonistic leptin variants and severe, early-onset obesity
| العنوان: | Rare antagonistic leptin variants and severe, early-onset obesity |
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| المؤلفون: | Funcke, Jan-Bernd, Moepps, Barbara, Roos, Julian, von Schnurbein, Julia, Verstraete, Kenneth, Fröhlich-Reiterer, Elke, Kohlsdorf, Katja, Nunziata, Adriana, Brandt, Stephanie, Tsirigotaki, Alexandra, Dansercoer, Ann, Suppan, Elisabeth, Haris, Basma, Debatin, Klaus-Michael, Savvides, Savvas, Farooqi, I. Sadaf, Hussain, Khalid, Gierschik, Peter, Fischer-Posovszky, Pamela, Wabitsch, Martin |
| المصدر: | NEW ENGLAND JOURNAL OF MEDICINE ; ISSN: 0028-4793 ; ISSN: 1533-4406 |
| سنة النشر: | 2023 |
| المجموعة: | Ghent University Academic Bibliography |
| مصطلحات موضوعية: | Biology and Life Sciences, Medicine and Health Sciences, BINDING-SITE-III, BETA-SUBUNIT, RECEPTOR, MUTATION, HYPOGONADISM, SUBSTITUTION, ACTIVATION, MECHANISM |
| الوصف: | Hormone absence or inactivity is common in congenital disease, but hormone antagonism remains controversial. Here, we characterize two novel homozygous leptin variants that yielded antagonistic proteins in two unrelated children with intense hyperphagia, severe obesity, and high circulating levels of leptin. Both variants bind to the leptin receptor but trigger marginal, if any, signaling. In the presence of nonvariant leptin, the variants act as competitive antagonists. Thus, treatment with recombinant leptin was initiated at high doses, which were gradually lowered. Both patients eventually attained near-normal weight. Antidrug antibodies developed in the patients, although they had no apparent effect on efficacy. No severe adverse events were observed. (Funded by the German Research Foundation and others.) |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://biblio.ugent.be/publication/01H7Z9GAGV5W60R4QDC3JN5TFHTest; http://hdl.handle.net/1854/LU-01H7Z9GAGV5W60R4QDC3JN5TFHTest; http://doi.org/10.1056/NEJMoa2204041Test; https://biblio.ugent.be/publication/01H7Z9GAGV5W60R4QDC3JN5TFH/file/01H7Z9M9955DHEXBQJV62GXNWGTest |
| DOI: | 10.1056/NEJMoa2204041 |
| الإتاحة: | https://doi.org/10.1056/NEJMoa2204041Test https://biblio.ugent.be/publication/01H7Z9GAGV5W60R4QDC3JN5TFHTest http://hdl.handle.net/1854/LU-01H7Z9GAGV5W60R4QDC3JN5TFHTest https://biblio.ugent.be/publication/01H7Z9GAGV5W60R4QDC3JN5TFH/file/01H7Z9M9955DHEXBQJV62GXNWGTest |
| حقوق: | No license (in copyright) ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.ED604802 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1056/NEJMoa2204041 |
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