The prevalence of melanocortin-4 receptor gene mutations in Slovak obese children and adolescents

Abstract

Melanocortin-4 receptor (MC4R) deficiency is the most frequent monogenic form of obesity. The contribution of MC4R mutations to the Slovak population has not been investigated as yet. We screened the coding sequence of the MC4R gene in a cohort of 210 Slovak obese children and adolescents. We identified four different mutations in four patients, giving a mutation detection rate of 0.95%. Of these, three were missense mutations previously identified and characterized by other research groups (p.R7C, p.S127L and p. R305W, respectively). One was a novel nonsense mutation p.W174* detected in a severely obese 7-year-old boy. This mutation was further analyzed in family segregation analysis and exhibited variable penetrance. Two known amino acid polymorphisms (p.V103I and p.I251L) were also identified in seven subjects of our cohort group. We also performed multifactorial statistical analysis to determine the influence of genotypes on standard biochemical blood markers. No significant influence was observed in carriers of DNA variants on tested parameters. We conclude that rare heterozygous MC4R mutations contribute to the onset of obesity only in a few cases in the Slovak population.

Melanocortin-4 Receptor Gene Mutations in a Group of Turkish Obese Children and Adolescents

“…However, the age of onset of obesity was significantly lower in mutation carriers compared to non-carriers. These findings were similar to those of other studies ( 7 , 13 , 14 , 19 ). In addition, hyperphagia, tall stature, and hyperinsulinemia were not present in all affected cases.…”

“…They have found three mutations in five obese children (1.6%) ( 14 ). Interestingly, frequency of MC4R mutations was only 0.95% among 210 Slovak children whose mean BMI SD score was 4.86±1.7 ( 7 ). However, Dubern et al ( 15 ) included 63 severely obese (BMI>SD score) French children with non-syndromic and early-onset obesity and found a higher prevalence: 6.3%.…”

“…However, we cannot make a comparison since definition of severe obesity and BMI values of the study group were not provided ( 17 ). Furthermore, it is known that some of the MC4R mutation carriers are obese during childhood but not in adulthood ( 7 , 14 , 18 ).…”

“…In addition, while both parents were heterozygous for the mutation, only the mother was obese. Several studies have also reported that mutation carriers would have a normal BMI value ( 7 , 14 , 18 ). According to Dubern et al ( 1 ), the phenotypic difference between the parents may be caused due to incomplete penetrance of mutations.…”

“…To date, over 150 different mutations have been reported in MC4R ( 4 ). Prevalence of MC4R mutations in children with severe obesity varies from 0.3% up to 6.3% ( 6 , 7 ). However, there is no such data from Turkey.…”