A Founder Mutation in the <i>POMC</i> 5′-UTR Causes Proopiomelanocortin Deficiency Through Splicing-Mediated Decrease of mRNA

The study identified a novel homozygous mutation in the 5'-untranslated region of the POMC gene in 7 unrelated patients from the Perm Tatar ethnic group, which caused proopiomelanocortin deficiency. This mutation, located at the splice donor site of intron 1, led to a significant decrease in POMC mRNA levels, contributing to symptoms such as hypoglycemia, excessive weight gain, low plasma adrenocorticotropin, and cortisol, with 5 of the 7 children having red hair. The mutation was suggested to have a founder effect, estimated to have occurred at least 4.27 generations ago. This research provided new insights into the molecular mechanisms and phenotypic variability of POMC deficiency.