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A frameshift mutation in human MC4R is associated with a dominant form of obesity

Nature Genetics volume 20, pages 113–114 (1998)Cite this article

Morbid obesity is characterized by a body mass index (BMI) greater than 40 kg/m2. It is a nutritional disease increasing in prevalence and is associated with multiple cardiovascular and metabolic complications. Although genetic factors are involved in the onset and progression of weight gain, most obesity susceptibility genes are unknown1.

The melanocortin-4 receptor (MC4R), is a seven transmembrane G-protein coupled receptor implicated in the central regulation of body weight2. Homozygous Mc4r-deficient mice display morbid obesity with hyperinsulinemia and heterozygote mice are also affected, displaying an intermediate phenotype3. MC4R, which is expressed in the hypothalamus, is activated by α-MSH, a neuropeptide derived from pro-opiomelanocortin2 and antagonized by agouti-related protein4 (ART/AGRP). This pathway is thought to be implicated in the central effects of leptin5.

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Figure 1: Mutation in MCR4 in patient Dz.
Figure 2: Pedigree, clinical characteristics and genotypes of the Dz family members.

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Acknowledgements

We thank G. Bonhomme, A. Legall and E. Rocca-Serra for cal help and C. Dina for statistical advice. This work was supported by the Direction de la Recherche Clinique/Assistance Publique-Hopitaux de Paris and the Programme Hospitalier de Recherche Clinique (PHRC). We obtained consent from all family members and ethical permission was granted by the local ethics committee (CCPPRB, Hôtel-Dieu, Paris).

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Authors and Affiliations

  1. Institut de Biologie-CNRS EP10, Institut Pasteur de Lille, rue Calmette 59000, Lille, France

    Christian Vaisse, Karine Clement, Bernard Guy-Grand & Philippe Froguel

  2. Laboratoire de Nutrition et Service de Médecine et Nutrition, Hôtel-Dieu place du Parvis Notre Dame 75004 , Paris, France

    Christian Vaisse, Karine Clement, Bernard Guy-Grand & Philippe Froguel

Authors
  1. Christian Vaisse
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  2. Karine Clement
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  3. Bernard Guy-Grand
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  4. Philippe Froguel
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Correspondence to Karine Clement.

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Vaisse, C., Clement, K., Guy-Grand, B. et al. A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat Genet 20, 113–114 (1998). https://doi.org/10.1038/2407

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