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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Melanocortin-4 receptor gene mutations in a Dutch cohort of obese children
Obesity, Volume 19, No. 3, Year 2011
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Description
The most common monogenic form of obesity is caused by mutations in the gene encoding the melanocortin-4 receptor (MC4R). We have screened the MC4R coding sequence in 291 patients of a Dutch outpatient pediatric obesity clinic. We analyzed the minimal promoter region of the gene in a random subgroup of 217 children. Our aims were (i) to determine the frequency of MC4R mutations in a cohort of Dutch clinically obese children and (ii) to search for mutations in the promoter of the gene. Eleven MC4R coding variants were detected. Five children had mutations that have been shown to affect receptor function by other research groups (p.Y35X, p.I251fs, p.G231S). These children did not have earlier onset of obesity or higher BMI-SDS than the remainder of the cohort. One child had a novel nonsynonymous coding mutation (p.L304F). This variant showed a markedly decreased cell surface expression in in vitro experiments and is thus expected to be pathogenic. We detected 12 variants in the MC4R flanking regions. Five of these were not previously described (c.-1101C>T, c.-705A>T, c.-461A>G, c.-312T>C, c.-213A>G). We investigated these mutations by family studies and a bioinformatic approach. We conclude that rare heterozygous mutations in the coding sequence of MC4R account for some severe obesity cases in the Dutch population. These patients are difficult to recognize in a clinical setting. We generated a list of all MC4R variants that were described in the literature so far, which can aid the interpretation of mutations found in a diagnostic setting. © 2010 The Obesity Society.
Authors & Co-Authors
Van Den Berg, Linda
Netherlands, Leiden
Leids Universitair Medisch Centrum
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Van Beekum, Olivier
Netherlands, Utrecht
Rudolf Magnus Institute of Neuroscience
Heutink, Peter
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Felius, Bram A.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Van De Heijning, Monique P.M.
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Strijbis, Stefan
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Van Spaendonk, Rosalina
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Piancatelli, Daniela
Italy, Rome
Consiglio Nazionale Delle Ricerche
Garner, Keith M.
Netherlands, Utrecht
Rudolf Magnus Institute of Neuroscience
El Aouad, Rajae
Morocco, Agdal Rabat
Institut National D'hygiène
Sistermans, Erik
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Adan, Roger A.H.
Netherlands, Utrecht
Rudolf Magnus Institute of Neuroscience
Delemarre-Van De Waal, H. A.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Statistics
Citations: 30
Authors: 13
Affiliations: 5
Identifiers
Doi:
10.1038/oby.2010.259
ISSN:
19307381
e-ISSN:
1930739X
Research Areas
Cancer
Genetics And Genomics
Health System And Policy
Maternal And Child Health
Noncommunicable Diseases
Study Design
Cross Sectional Study
Cohort Study