scholarly journals Melanocortin-4 Receptor Gene Mutations in Obese Slovak Children

2015 ◽  
pp. 883-890 ◽  
Author(s):  
D. STANIKOVA ◽  
M. SUROVA ◽  
L. TICHA ◽  
M. PETRASOVA ◽  
D. VIRGOVA ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
Dna Analysis ◽  
Receptor Gene ◽  
Gene Mutations ◽  
Loss Of Function ◽  
Obese Children ◽  
Mc4r Gene ◽  
Melanocortin 4 Receptor ◽  
Melanocortin 4 Receptor Gene ◽  
Common Etiology

The most common etiology of non-syndromic monogenic obesity are mutations in gene for the Melanocortin-4 receptor (MC485) with variable prevalence in different countries (1.2-6.3 % of obese children). The aim of our study was 1) to search for MC4R mutations in obese children in Slovakia and compare their prevalence with other European countries, and 2) to describe the phenotype of the mutation carriers. DNA analysis by direct Sanger sequencing of the coding exons and intron/exon boundaries of the MC4R gene was performed in 268 unrelated Slovak children and adolescents with body mass index above the 97th percentile for age and sex and obesity onset up to 11 years (mean 4.3±2.8 years). Two different previously described heterozygous loss of function MC4R variants (i.e. p.Ser19Alafs*34, p.Ser127Leu) were identified in two obese probands, and one obese (p.Ser19Alafs*34), and one lean (p.Ser127Leu) adult family relatives. No loss of function variants were found in lean controls. The prevalence of loss-of-function MC4R variants in obese Slovak children was 0.7 %, what is one of the lowest frequencies in Europe.

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

2017 ◽  
Vol 9 (3) ◽  
pp. 216-221 ◽  
Author(s):  
Selma Tunç ◽  
Korcan Demir ◽  
Fatma Ajlan Tükün ◽  
Cihan Topal ◽  
Filiz Hazan ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Receptor Gene ◽  
Gene Mutations ◽  
Obese Children ◽  
Melanocortin 4 Receptor ◽  
Melanocortin 4 Receptor Gene

Melanocortin-4 Receptor Gene Mutations in a Dutch Cohort of Obese Children

Obesity ◽  
2011 ◽  
Vol 19 (3) ◽  
pp. 604-611 ◽  
Author(s):  
Linda van den Berg ◽  
Olivier van Beekum ◽  
Peter Heutink ◽  
Bram A. Felius ◽  
Monique P.M. van de Heijning ◽  
...  
Keyword(s):  
Receptor Gene ◽  
Gene Mutations ◽  
Obese Children ◽  
Melanocortin 4 Receptor ◽  
Melanocortin 4 Receptor Gene ◽  
Dutch Cohort

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

2016 ◽  
Vol 29 (1) ◽  
Author(s):  
Emil Polák ◽  
Eva Vitáriušová ◽  
Peter Celec ◽  
Zuzana Pribilincová ◽  
Ľudmila Košťálová ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Receptor Gene ◽  
Gene Mutations ◽  
Obese Children ◽  
Monogenic Form ◽  
Melanocortin 4 Receptor ◽  
Melanocortin 4 Receptor Gene

AbstractMelanocortin-4 receptor (MC4R) deficiency is the most frequent monogenic form of obesity. The contribution of

Novel melanocortin 4 receptor gene mutations in severely obese children

2008 ◽  
Vol 68 (4) ◽  
pp. 529-535 ◽  
Author(s):  
Yung Seng Lee ◽  
Larry Kok Seng Poh ◽  
Betty Lay Kee Kek ◽  
Kah Yin Loke
Keyword(s):  
Receptor Gene ◽  
Gene Mutations ◽  
Obese Children ◽  
Melanocortin 4 Receptor ◽  
Melanocortin 4 Receptor Gene ◽  
Severely Obese

Melanocortin-4 Receptor Gene Variation Is Associated with Eating Behavior in Chilean Adults

2015 ◽  
Vol 68 (1) ◽  
pp. 35-41 ◽  
Author(s):  
Javier A. Vega ◽  
Gloria Salazar ◽  
María Isabel Hodgson ◽  
Luis Rodrigo Cataldo ◽  
Macarena Valladares ◽  
...  
Keyword(s):  
Eating Behavior ◽  
Emotional Eating ◽  
Leptin Receptor ◽  
Receptor Gene ◽  
Pathogenic Mutation ◽  
Gene Variation ◽  
Mc4r Gene ◽  
Melanocortin 4 Receptor ◽  
Melanocortin 4 Receptor Gene ◽  
Mc4r Rs17782313

Background/Aims: To evaluate the association between allelic variants of melanocortin receptors -3 and -4 (MC3R and MC4R, respectively) and leptin receptor (LEPR) genes with body mass index (BMI) and eating behavior. Methods: We selected 344 Chilean adults (57.8% women; age 39.1 ± 6.6 years) with a wide variation in BMI (30.3 ± 6.3 kg/m2). The Three-Factor Eating Questionnaire-R18 that measures uncontrolled eating (UE), emotional eating (EE) and cognitive restraint scores was adapted, validated and assessed for association with BMI. Genotypes were determined by polymerase chain reaction followed by restriction fragment length polymorphism techniques and Taqman assays. Results: Higher EE scores were found in obese vs. non-obese in both men (p = 0.01) and women (p < 0.001). UE scores were significantly associated with BMI only in women (p = 0.002). No significant differences in eating behavior scores or BMI were found by LEPR (rs1137101, rs8179183 and rs1137100 polymorphisms) or MC3R (rs3746619 and rs3827103). Carriers of the C allele for MC4R rs17782313 showed significantly higher scores of UE compared to non-carriers (2.3 ± 0.8 vs. 2.0 ± 0.7; p = 0.02). Additionally, we also report a monogenic case of obesity carrying the pathogenic mutation 449C>T (Thr150Ile) in MC4R gene with no apparent alterations in eating behavior scores. Conclusions: UE scores were higher in C-allele carriers of MC4R-rs17782313 compared to non-carriers.

A Novel Loss of Function Melanocortin-4-Receptor Mutation (MC4R-F313Sfs*29) in Morbid Obesity

2020 ◽  
Author(s):  
Elisabetta Trevellin ◽  
Marnie Granzotto ◽  
Cristina Host ◽  
Francesca Grisan ◽  
Diego De Stefani ◽  
...  
Keyword(s):  
Early Onset ◽  
Functional Characterization ◽  
Gene Mutations ◽  
Melanocortin Receptor ◽  
Hek293 Cells ◽  
Intracellular Camp ◽  
Loss Of Function ◽  
Mc4r Gene ◽  
Melanocortin 4 Receptor

Abstract Context Melanocortin receptor-4 (MC4R) gene mutations are associated with early-onset severe obesity, and the identification of potential pathological variants is crucial for the clinical management of patients with obesity. Objective To explore whether and how a novel heterozygous MC4R variant (MC4R-F313Sfs*29), identified in a young boy (body mass index [BMI] 38.8 kg/m2) during a mutation analysis conducted in a cohort of patients with obesity, plays a determinant pathophysiological role in the obesity development. Design Setting and Patients The genetic screening was carried out in a total of 209 unrelated patients with obesity (BMI ≥ 35 kg/m2). Structural and functional characterization of the F313Sfs*29-mutated MC4R was performed using computational approaches and in vitro, using HEK293 cells transfected with genetically encoded biosensors for cAMP and Ca2+. Results The F313Sfs*29 was the only variant identified. In vitro experiments showed that HEK293 cells transfected with the mutated form of MC4R did not increase intracellular cAMP or Ca2+ levels after stimulation with a specific agonist in comparison with HEK293 cells transfected with the wild type form of MC4R (∆R/R0 = -90% ± 8%; P &lt; 0.001). In silico modeling showed that the F313Sfs*29 mutation causes a major reorganization in the cytosolic domain of MC4R, thus reducing the affinity of the putative GalphaS binding site. Conclusions The newly discovered F313Sfs*29 variant of MC4R may be involved in the impairment of α-MSH-induced cAMP and Ca2+ signaling, blunting intracellular G protein-mediated signal transduction. This alteration might have led to the dysregulation of satiety signaling, resulting in hyperphagia and early onset of obesity.

scholarly journals Sympathetic Function in Human Carriers of Melanocortin-4 Receptor Gene Mutations

2010 ◽  
Vol 95 (4) ◽  
pp. 1998-2002 ◽  
Author(s):  
Friedhelm Sayk ◽  
Dennis Heutling ◽  
Christoph Dodt ◽  
K. Alexander Iwen ◽  
J. Peter Wellhoner ◽  
...  
Keyword(s):  
Receptor Gene ◽  
Gene Mutations ◽  
Sympathetic Function ◽  
Melanocortin 4 Receptor ◽  
Melanocortin 4 Receptor Gene
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