Screening for melanocortin-4 receptor mutations in a cohort of Belgian morbidly obese adults and children

Abstract

Objective: To investigate whether pathogenic melanocortin-4 receptor (MC4R) mutations are a common cause of obesity in Belgium. Design: Cross-sectional mutation analysis. Subjects: In total, 95 morbidly obese adults (mean age 44.02711.35 years; mean BMI 47.8774.17 kg/m 2 ) and 123 obese children and adolescents were screened for mutations in MC4R (mean age 16.5672.58 years; BMI495th percentile for age and sex; mean % overweight 170.86723.63). Measurements: A series of anthropometric (e.g. weight, height, waist, hip), biochemical and clinical measurements were performed on all subjects. The entire coding region of MC4R was screened using DHPLC, a highly sensitive and specific method for mutation analysis. Direct sequencing was performed when the chromatogram deviated from the WT pattern. Results: Mutation screening of a cohort of Belgian obese adults and children did not detect any pathogenic mutations as only the previously described polymorphisms Val103Ile, Thr112Met and Ile251Leu were detected. Conclusion: Pathogenic mutations in MC4R are not a common cause of obesity in a Belgian population of obese adults, children and adolescents.

Novel Variants in theMC4RandLEPRGenes among Severely Obese Children from the Iberian Population

“…More than 150 variants of this gene have been described as leading to decreased MC4R activity associated with human obesity and are usually classified into different classes depending on their molecular characteristics (Hinney et al, 2013). The prevalence of severe obesity associated with mutations in this pathway is estimated to be around 2.5% (Beckers et al, 2006). Hence, among children with severe and early-onset obesity, screening for mutations in the MC4R and LEPR genes could be the first step to determine inherited susceptibility as the main and genetically conditioned causes of the overweight.…”

“…The 38-year-old mother presented with morbid obesity since childhood, reaching a maximum weight when she was 23 years old (200 kg, BMI: 75 kg/m 2 ); she had undergone bariatric surgery. While segregation analyses in pedigree F suggest that the p.I251L mutation can be involved in the daughter's and father's obese phenotypes, data in the literature showed the p.I251L substitution with polymorphic frequencies in several general populations, with similar frequencies in obese and control subjects (Beckers et al, 2006). Moreover, the complete gene sequencing failed to show MC4R mutations in the mother with morbid obesity that is therefore likely to be associated with different genetic alterations.…”

Current review of genetics of human obesity: from molecular mechanisms to an evolutionary perspective

“…In 1998, two independent groups reported a mutation in the MC4R gene, which result in a non-functional receptor causing severe early-onset obesity (Vaisse et al 1998;Yeo et al 1998). In morbidly obese individuals, deficiency in the MC4R gene activity represents the most common cause (1 to 6%) for the obese phenotype (Yeo et al 1998;Farooqi et al 2003;Beckers et al 2006). More than 150…”

Identification and functional characterization of a missense mutation in resistin in two patients with severe obesity and insulin resistance

“…Sequencing was performed with ABI BigDye Terminator v1.1 Cycle Sequencing kits on an ABI Prism Genetic Analyzer 3130xl (Applied Biosystems, Inc., Foster City, USA). The melanocortin-4 receptor gene (MC4R) was screened as described before (29). Primer sequences for mutation analysis of RETN are as follows: exon 2 DHPLC forward 5 0 -gTTcccTcTTTcAgcgccTgc-3 0 …”