A Novel Homozygous Missense Mutation of Melanocortin-4 Receptor (MC4R) in a Japanese Woman With Severe Obesity

• DOI: 10.2337/diabetes.51.1.243
• Publication Date: 2007-03-06T19:04:22Z
• Authors: Hiromasa Kobayashi; Yoshihiro Ogawa; Mitsuyo Shintani; Ken Ebihara; Makiko Shimodahira; Toshio Iwakura; Megumu Hino; Takashi Ishihara; Katsuji Ikekubo; Hiroyuki Kurahachi; Kazuwa Nakao
• Keywords: Melanocortin 4 receptor

The melanocortin-4 receptor (MC4R) is a member of the seven membrane-spanning G protein-coupled superfamily and signals through activation adenylyl cyclase. MC4R mutations are most common known monogenic cause human obesity. However, no such have been found in Japanese obese subjects. Here we report novel homozygous missense mutation (G98R) nondiabetic woman with severe early-onset obesity, which located its second transmembrane domain. Her birth weight was 3,360 g, she gained progressively from 10 months age. At 40 years age, her reached 160 kg BMI 62 kg/m(2). parents, who heterozygous for mutation, BMIs 26 27 In vitro transient transfection assays revealed discernable agonist ligand binding cAMP production HEK293 cells expressing mutant receptor, indicating loss-of-function mutation. This study represents first demonstration pathogenic Japan will provide further insight into pathophysiologic role hypothalamic melanocortin system