These findings align with those reported for other obesity-associated genes (MRAP2, KSR2, and PHIP) (10, 21, 22), where rare heterozygous variants are associated with obesity but are not always causative, in contrast to the classical monogenic obesity syndromes that follow an autosomal recessive (LEP, LEPR, POMC, and PCSK1) or dominant (MC4R, SIM1, and GNAS) mode of inheritance (1). This evidence concerns the gene SIM1 and obesity due to melanocortin 4 receptor deficiency.