ESPE Abstracts

Background: Obesity is a multifactorial disease caused by environmental and genetic factors. Single gene defects explain approximately 5-13% of early-onset obesity and these rates vary according to genetic panel used and the rate of consanguinity in the population studied. As the new treatment modalities emerge for monogenic obesity, it is important to identify the molecular etiology of obesity.

Materials and Methods: Buccal swab samples were taken for genetic analysis from 27 obese chidren with a body mass index of over 120% and a history of early-onset obesity (<5 years old) between August 2022 and January 2023. ROAD gene panel containing 79 genes and 1 chromosome region. (ADCY3, AFF4, ALMS1, ARL6, BBIP1, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, BDNF, CEP290, CFAP418, CPE, CREBBP, CUL4B, DNMT3A, DYRK1B, EP300, GNAS, HTR2C, IFT172, IFT27, IFT74, INPP5E, ISL1, KIDINS220, KSR2, LEP, LEPR, LZTFL1, MAGEL2, MC3R, MC4R, MECP2, MKKS, MKS1, MRAP2, NCOA1, NR0B2, NRP1, NRP2, NTRK2, PCNT, PCSK1, PHF6, PHIP, PLXNA1, PLXNA2, PLXNA3, PLXNA4, POMC, PPARG, PROK2, RAB23, RAI1, RPGRIP1L, RPS6KA3, SDCCAG8, SEMA3A, SEMA3B, SEMA3C, SEMA3D, SEMA3E, SEMA3F, SEMAB3G, SH2B1, SIM1, TBX3, TRIM32, TRPC5, TTC8, TUB, UCP3, VPS13B, WDPCP + 16p11.2) were applied to these samples. Segregation analyses were performed in patients who had variations classified as unknown clinical significance(VUS), likely pathogenic(LP) and pathogenic acccording to ACMG classification.

Results: The mean age of 24 patients (50% male)whose analyzes were completed was 12.64 years. While no variation was detected in 8 of the patients, 30 changes were detected in 17 genes in 18 patients. While 5 of them were classified as benign or likely benign, 18 (58.6%) were classified as VUS, 4 as likely pathogenic (13.7%), and 3 as pathogenic (10.3%). More than one variation was detected in eight cases. All variants were heterozygous. In 6 of the index patients whose results were completed, LEPR, PCSK1, PLXNA2, PLXNA3, GNAS mutations and dup(19)(q13.2)chr19 were detected as the etiology of obesity. Detection rate of a monogenic cause in our cohort was 25%.

Conclusion:A monogenic cause for obesity was detected in approximately one in every four children with early-onset obesity in our cohort which is higher then previously reported cohorts.