Sporadic mutations in melanocortin receptor 3 in morbid obese individuals

Monica Mencarelli, Gillian E. Walker, Sabrina Maestrini, Luisella Alberti, Barbara Verti, Amelia Brunani, Maria Letizia Petroni, Mariantonella Tagliaferri, Antonio Liuzzi, Anna Maria Di Blasio

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Abstract

Several mutations in the melanocortin receptor 4 gene have been identified in humans and account for 3-6% of morbid obesity. In contrast, strong evidence of a causative role for melanocortin receptor 3 (MC3R) mutations are still lacking. In MC3R knockout mice, high feed efficiency rather than hyperphagia seems to contribute to increased fat mass. On the basis of this evidence, the objective of the present study was to investigate the presence of MC3R mutations in a group of 290 obese subjects (mean BMI 44.2 ± 5.9kg/m2). As a control, a group of 215 normal-weight subjects (mean BMI 22.4 ± 2.7kg/m2) was also screened. Three novel mutations in the MC3R gene (A293T, I335S and X361S) were identified among the obese patients. The mutations segregated with obesity in the members of the families studied. In vitro expression studies of each mutation demonstrated a loss of function of the I335S-mutated receptor. These findings suggest that, in humans, MC3R mutations may be a cause of a dominantly inherited form of obesity. However, this association as well as the specific phenotypic characteristics resulting from these mutations need to be further evaluated in larger series of obese subjects.

Original languageEnglish
Pages (from-to)581-586
Number of pages6
JournalEuropean Journal of Human Genetics
Volume16
Issue number5
DOIs
Publication statusPublished - May 2008

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Receptor, Melanocortin, Type 3
Mutation
Obesity
Receptor, Melanocortin, Type 4
Hyperphagia
Morbid Obesity
Knockout Mice
Genes
Fats
Weights and Measures

ASJC Scopus subject areas

  • Genetics(clinical)

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Sporadic mutations in melanocortin receptor 3 in morbid obese individuals. / Mencarelli, Monica; Walker, Gillian E.; Maestrini, Sabrina; Alberti, Luisella; Verti, Barbara; Brunani, Amelia; Petroni, Maria Letizia; Tagliaferri, Mariantonella; Liuzzi, Antonio; Di Blasio, Anna Maria.

In: European Journal of Human Genetics, Vol. 16, No. 5, 05.2008, p. 581-586.

Research output: Contribution to journalArticle

Mencarelli, Monica ; Walker, Gillian E. ; Maestrini, Sabrina ; Alberti, Luisella ; Verti, Barbara ; Brunani, Amelia ; Petroni, Maria Letizia ; Tagliaferri, Mariantonella ; Liuzzi, Antonio ; Di Blasio, Anna Maria. / Sporadic mutations in melanocortin receptor 3 in morbid obese individuals. In: European Journal of Human Genetics. 2008 ; Vol. 16, No. 5. pp. 581-586.
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