Genotype-Phenotype Spectrum of Non-Syndromic Monogenic Obesity in a National Paediatric Cohort.

Biallelic (LEP, LEPR, POMC, PCSK1, MC4R, ADCY3) or monoallelic (MC4R) variants → satiety and energy expenditure dysregulation

130 children with non-syndromic monogenic obesity were recruited from 23 Turkish pediatric endocrinology centers. Biallelic LEPR (n=47) and monoallelic MC4R (n=49) are the most frequent causes. BMI-SDS is higher in LEP, LEPR, and biallelic MC4R forms. The SPISE index (insulin resistance proxy) differs significantly between groups, providing a metabolic stratification tool complementary to genotype.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

This national Turkish cohort is one of the largest published for non-syndromic monogenic obesity and illustrates the diagnostic value of WES in early-onset severe obesity. The genotype-metabolic profile correlation could guide therapeutic choices (e.g., setmelanotide for POMC/LEPR) — a rapidly expanding field.

Clinical impact: 2/3 · Evidence strength: 2/3 · Novelty: 1/2 · Sample size: 1/1 · Publication status: 0/1 → Total: 6/10