Identification of a novel leptin receptor (LEPR) variant and proof of functional relevance directing treatment decisions in patients with morbid obesity

Deficiency in the leptin-leptin receptor (LEPR) axis leads to severe, and potentially treatable, obesity in humans. To guide clinical decision-making, the functional relevance of variants in the LEPR gene needs to be carefully investigated.Cases and methods.We characterized the functional impact of LEPR variants identified in two cases with severe early-onset obesity (1: compound heterozygous for the novel variant p.Tyr411del and p.Trp664Arg; 2: heterozygous for p.Arg612His) by investigating leptin-mediated signaling, leptin binding, receptor expression on cell surfaces, and receptor dimerization and activation for either wild-type and/or mutant LEPR.

Source: Metabolism - Clinical and Experimental - November 19, 2020 Category: Biomedical Science Authors: Franziska Voigtmann, Philipp Wolf, Kathrin Landgraf, Robert Stein, J ürgen Kratzsch, Samuel Schmitz, Rami Abou Jamra, Matthias Blüher, Jens Meiler, Annette G. Beck-Sickinger, Wieland Kiess, Antje Körner Source Type: research