A fresh look to the phenotype in mono-allelic likely pathogenic variants of the leptin and the leptin receptor gene

AbstractLeptin (LEP) and leptin receptor (LEPR) play a major role in energy homeostasis, metabolism, and reproductive function. While effects of biallelic likely pathogenic variants (-/-) on the phenotype are well characterized, effects of mono-allelic likely pathogenic variants (wt/-) in theLEP andLEPR gene on the phenotype compared to wild-type homozygosity (wt/wt) have not been systematically investigated. We identified in our systematic review 44 animal studies (15 onLep, 29 onLepr) and 39 studies in humans reporting on 130 mono-allelic likely pathogenic variant carriers with 20 distinctLEP variants and 108 heterozygous mono-allelic likely pathogenic variant carriers with 35 distinctLEPR variants. We found indications for a higher weight status in carriers of mono-allelic likely pathogenic variant in the leptin and in the leptin receptor gene compared towt/wt, in both animal and human studies. In addition, animal studies showed higher body fat percentage inLep andLepr wt/- vswt/wt. Animal studies provided indications for lower leptin levels inLep wt/- vs.wt/wt and indications for higher leptin levels inLepr wt/- vswt/wt. Data on leptin levels in human studies was limited. Evidence for an impaired metabolism in mono-allelic likely pathogenic variants of the leptin and in leptin receptor gene was not conclusive (animal and human studies). Mono-allelic likely pathogenic variants in the leptin and in leptin receptor gene have phenotypic effects disposing to increased body wei...
Source: Molecular and Cellular Pediatrics - Category: Cytology Source Type: research