We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Severe Early-Onset Obesity Due to Bioinactive Leptin Caused by a p.N103K Mutation in the Leptin Gene.
- Authors
Wabitsch, Martin; Funcke, Jan-Bernd; von Schnurbein, Julia; Denzer, Friederike; Lahr, Georgia; Mazen, Inas; El-Gammal, Mona; Denzer, Christian; Moss, Anja; Debatin, Klaus-Michael; Gierschik, Peter; Mistry, Vanisha; Keogh, Julia M; Farooqi, I Sadaf; Moepps, Barbara; Fischer-Posovszky, Pamela
- Abstract
<bold>Context: </bold>Congenital leptin deficiency is a very rare cause of severe early-onset obesity. We recently characterized a mutation in the leptin gene (p.D100Y), which was associated with detectable leptin levels and bioinactivity of the hormone.<bold>Case Description: </bold>We now describe two siblings, a 9-year-old girl and a 6-year-old boy with severe early-onset obesity and hyperphagia, both homozygous for a c.309C>A substitution in the leptin gene leading to a p.N103K amino acid exchange in the protein and detectable circulating levels of leptin. In vitro experiments in a heterologous cell system demonstrated that the mutated protein was biologically inactive. Treatment with sc recombinant human leptin led to rapid improvement of eating behavior and weight loss.<bold>Conclusions: </bold>Sequencing of the leptin gene may need to be considered in hyperphagic, severely obese children with detectable levels of circulating leptin.
- Publication
Journal of Clinical Endocrinology & Metabolism, 2015, Vol 100, Issue 9, p3227
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2015-2263