Although body weight is largely determined by lifestyle factors, increasingly research is revealing that genetics also play an important role in determining an individual's susceptibility to obesity. Identifying the mutations that underlie the fraction of obese patients with monogenic obesity can help us to understand complex processes like metabolic rate, eating behavior, growth, and fat storage. In this issue of the Journal of Clinical Investigation , two groups identified obesity-linked mutations in the gene SIM1 . Sadaf Farooqi and colleagues at Addenbrooke's Hospital in Cambridge, England, identified thirteen SIM1 mutations in obese patients, and found that reduced SIM1 function correlated with increased food intake and altered nervous system dysfunction. In an independent study, Philippe Froguel and colleagues at Imperial College London identified eight SIM1 mutations in morbidly obese adults and in patients with a disorder resembling Prader-Willi syndrome. In the patients studied, loss of SIM1 function was associated with inherited obesity. Taken together, these studies confirm a strong link between SIM1 dysfunction and obesity.
TITLE: Rare variants in single-minded 1 ( SIM1 ) are associated with severe obesity
AUTHOR CONTACT: Sadaf Farooqi
Addenbrooke's Hospital, Cambridge, GBR
Phone: 44-1223-762-634; Fax: 44-1223-762-657; E-mail: isf20@cam.ac.uk
View this article at: http://www.jci.org/articles/view/68016?key=feaa61c9a393337a621e
ACCOMPANYING ARTICLE
TITLE: Loss-of-function mutations in SIM1 contribute to obesity and Prader-Willi-like features
AUTHOR CONTACT: Philippe Froguel
Imperial College London, London, GBR
Phone: +44 (0)20 8383 3989; Fax: +33-320.87.7229; E-mail: p.froguel@imperial.ac.uk
View this article at: http://www.jci.org/articles/view/68035?key=f88789a26f0ff48e9899
Journal of Clinical Investigation