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Open Access 01-12-2021 | Review

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

Authors: Ingrid Koerber-Rosso, Stephanie Brandt, Julia von Schnurbein, Pamela Fischer-Posovszky, Josef Hoegel, Hannah Rabenstein, Reiner Siebert, Martin Wabitsch

Published in: Molecular and Cellular Pediatrics | Issue 1/2021

Abstract

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.

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Title: A fresh look to the phenotype in mono-allelic likely pathogenic variants of the leptin and the leptin receptor gene
Authors: Ingrid Koerber-Rosso
Stephanie Brandt
Julia von Schnurbein
Pamela Fischer-Posovszky
Josef Hoegel
Hannah Rabenstein
Reiner Siebert
Martin Wabitsch
Publication date: 01-12-2021
Publisher: Springer Berlin Heidelberg
Published in: Molecular and Cellular Pediatrics / Issue 1/2021
Electronic ISSN: 2194-7791
DOI: https://doi.org/10.1186/s40348-021-00119-7

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

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