Rare variants in the LEPR gene identified in three patients with severe early-onset obesity and hyperphagia

Abstract

   Congenital leptin receptor deficiency (LEPR) is a rare monogenic form of severe early-onset obesity. This study presents new pathogenic variants in the LEPR gene identified in Russian patients with early-onset severe obesity. Two rare variants were discovered: c.133_136dup in a homozygous state in two patients and a variant in a compound heterozygous state with a novel variant c.2590_2591del in a third patient. Both variants cause the synthesis of non-functional leptin receptors, which is characteristic of autosomal recessive LEPR deficiency. The results expand the spectrum of known LEPR variants and emphasize the importance of genetic testing when monogenic forms of obesity are suspected.