POMC and Obesity: Loss-of-function mutations [e.g., a homozygous mutation (C3804A) in exon 2 (now exon 3) and a compound heterozygote for two mutations (G7013T and 1 bp-deletion C7133Δ) in exon 3 (now exon 4)], resulting in ACTH and α-MSH deficiency, caused severe early-onset obesity, adrenal insufficiency and red hair pigmentation [24].