The first PCSK1 mutation, a compound heterozygous mutation, was identified in 1997, in a patient with obesity and hypogonadotropic hypogonadism (Gly483Arg and a donor splice site mutation in intron 5, causing skipping of exon 5 and the creation of a premature stop codon) [87]. Here, PCSK1 is linked to obesity due to melanocortin 4 receptor deficiency.