Background: Mutations in the melanocortin 4 receptor ( MC4R) gene are the most frequent cause of monogenic forms of obesity, but the reported prevalences of mutations in obese individuals diverge, varying from 0.2 to 5.8%.
Objective: The aim of this study was to assess the prevalence of MC4R mutations in obese children and adults residing in Norway.
Subjects and methods: We sequenced the coding region of MC4R in 1 027 obese patients. Among these, were 644 adults with a BMI >35 kg/m(2) and 383 children with a body weight >97.5 percentile for height. Identified mutations were analyzed by family studies and a bioinformatic approach including comparative sequence analysis and prediction of impact on transmembrane helix and three dimensional structure.
Results: Nine mutations were identified, of which four were novel and five previously described. The prevalence of MC4R mutations was 1.6% in pediatric and 0.8% in adult patients. All four novel mutations, I69R, M79I, I195S, and M200del were identified among pediatric patients. M79I was found in an ethnic Norwegian patient, while the rest were identified in second generation immigrants. The previously described mutations Y35X/D37V, V95I, T150I, R236C and V253I were identified in one pediatric and five adult patients. None of the adult patients reported childhood onset of obesity. The M200del mutation was found in a homozygous state, while the rest were heterozygous.
Conclusion: MC4R mutations are not a common cause of obesity in Norway and screening of obese patients does not appear to be warranted. The results are consistent with results from previous studies.