A New Mutation Has Been Identified and a New Molecular Mechanism for Developing Pro-opiomelanocortin Deficiency Has Been Described

Pro-opiomelanocortin (POMC) deficiency is clinically manifested by obesity, adrenal failure, and red hair color (Obesity, Adrenal Insufficiency and Red Hair Syndrome, OBAIRH syndrome, MIM# 609734). The disease is associated with mutations in the POMC gene and makes its debut in the first months of life with symptoms of severe hypoglycemia. To date, the literature has described fewer than 50 patients with this pathology. 

The article which is devoted to the teamwork of specialists of the National Medical Research Centre for Endocrinology and the Research Centre for Medical Genetics was published in «The Journal of Clinical Endocrinology and Metabolism». 

POMC deficiency was suspected in NMRC for Endocrinology in 7 unrelated ethnically Permian Tatar patients with typical symptoms, but no changes were found in the coding sequence of the POMC gene. Subsequent research using full-exome sequencing, as well as analysis of regions of autozygosity, revealed a common homozygous mutation in the untranslated region of the POMC gene. The variant had not been previously described and a functional analysis was performed in the functional genomics laboratory of RCMG to determine its pathogenicity. It was performed in vitro using minigene technology, it demonstrated a marked decrease in the expression of the matrix RNA of the POMC gene. The founder effect was also shown for the new mutation. 

Thus, the scientific work demonstrated a new molecular mechanism for developing pro-opiomelanocortin deficiency. The proven pathogenicity of the identified mutation also opens prospects for pathogenetic therapy of patients with this pathology.