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

Molecular and Cellular Pediatrics

Martin Wabitsch¹  Julia von Schnurbein¹  Stephanie Brandt¹  Pamela Fischer-Posovszky¹  Ingrid Koerber-Rosso¹  Hannah Rabenstein²  Reiner Siebert²  Josef Hoegel² 

[1] Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany;Institute of Human Genetics, University of Ulm, University Medical Center Ulm, Ulm, Germany;

关键词: LEP;    LEPR;    Phenotype;    Animal;    Humans;   

DOI  :  10.1186/s40348-021-00119-7

来源: Springer

【 摘 要 】

Leptin (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 the LEP and LEPR 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 on Lep, 29 on Lepr) and 39 studies in humans reporting on 130 mono-allelic likely pathogenic variant carriers with 20 distinct LEP variants and 108 heterozygous mono-allelic likely pathogenic variant carriers with 35 distinct LEPR 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 to wt/wt, in both animal and human studies. In addition, animal studies showed higher body fat percentage in Lep and Lepr wt/- vs wt/wt. Animal studies provided indications for lower leptin levels in Lep wt/- vs. wt/wt and indications for higher leptin levels in Lepr wt/- vs wt/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 weight and fat accumulation.

【 授权许可】

CC BY