Identification and Characteristics of Novel Mutations in Nonsyndromic Monogenic Obesity

Abstract Nonsyndromic monogenic obesity (NSMO) is a class of individual obesity that is independent of the environment and caused by a single gene mutation. It is mostly caused by mutations in LEP, LEPR, PCSK1 , as well as some rare mutations in UCP3, NR0B2 , and PPARG . Among 30 obesity patients, five patients are identified with positive gene detection. For the first time, the c.624C>T mutation associated with PCSK1 , and the c.50G>A and c.293_301delinsAC mutations associated with NR0B2 , as well as the obesity phenotype mutation (c.284A>G) associated with PPARG is confirmed. Following this, the genotype‐clinical phenotype, mutation hotspots, and mutation distributions of each gene are summarized, and the genetic characteristics of NSMO are analyzed. The locations of mutation c.50G>A, and c.284A>G are highly conserved according to the sequencing alignment. According to the findings, the c.624C>T mutation in PCSK1 is a newly discovered synonymous mutation, but it can result in significant early‐onset obesity. Additionally, the mutation of c.284A>G( PPARG ) can lead to a variety of clinical phenotypes and the mutation of UCP3 and NR0B2 may increase the risk of type 2 diabetes mellitus. This study enriches the human NSMO gene mutation database and provides a scientific basis for clinically accurate diagnosis and treatment.