P-242: Results of the first molecular study of monogenic obesity at Elizalde’s children hospital in Buenos Aires city, Argentina
E A San Martin, J Serra, M Franciulli, M E Andres, M Silberkasten, L Braguinsky, N Grimberg, V M Jimenez, A Franchello, V BrittoAbstract
Introduction
Monogenic syndromic and non-syndromic obesity are a rare form of severe early-onset obesity. They are associated with dysfunction in the leptin-melanocortin pathway in the hypothalamus, which is responsible for regulating energy balance. Non-syndromic monogenic obesity can be a challenge to diagnose from other causes of severe obesity without genetic testing. Currently, specific treatments exist for some of these conditions
Objectives
Report the results of a genetic diagnosis program with a genetic panel for obesity in children with early onset severe obesity and hyperphagia in Pedro de Elizalde’s Children Hospital in Argentina
Methods
Retrospective, descriptive, cross-sectional study from clinical records review. Inclusion criteria: children with BMI SD >3 and early onset obesity plus hyperphagia were screened between June 2021 and November 2025 by a next-generation sequencing based, targeted DNA custom panel for 79 known-obesity-related genes and 16p11.2 chromosomal region. Ethical considerations: the study was approved by Elizalde’s Children Hospital ethics committee
Results
A total of 164 patients were included. Mean age 8.9 ± 4.9 years (range 0.5-19 years), Mean BMI 32.8 ± 8.8 (range 11.7–68.2), Mean BMI-Z score: 4.78. In 30 patients did not have detected variants (18.29 %), 134 patients did have detected variants (81.70 %). 212 variants were detected: 191 were uncertain variants and 21 pathogenic or likely pathogenic. Gen and genomic coordinates that showed pathogenic or likely pathogenic variants were: arr[GRCh37], CEP290, BBS2, ARL6, MECP2, GNAS, MC4R, BBS4, IFT172, KIDINS220, ALMS, BBS9 and arr[hg19]. Among the 191 uncertain variants detected, the most frequent variants were: PCNT, ALMS1, NRP2, CEP290 and PLXNA3.
Conclusions
81.70% of the panels showed genetic variants. 10 variants were pathogenic and 11 likely pathogenic. This study is part of a broader project to better define the prevalence of these genetic variants and find genotype/phenotype correlations.