Genetic Evaluation of a Hereditary Familial Severe Obesity Due to Naturally Occurring Mutation in the Leptin Receptor and Structure Homology Modelling of the Mutated Molecule

Obesity, a growing universal problem, is a disorder/illness related to several factors. These factors are including environmental, metabolic and genetic factors. Genetic studies have been undertaken for several different causative mutations involving obesity genes on different chromosomes and few mutations have been reported in that regard. Leptin is one of the most important adipose derived hormones with important role in regulating body weight through the inhibition of food intake and stimulation of energy expenditure. This hormone binds to leptin receptor that is present in surface of a number of cells especially to the ventromedial nucleus of the hypothalamus, known as the appetite centre, and it can activate intracellular signalling domains. A very small group of humans possess homozygous mutations for the leptin/ leptin receptor genes which lead to a constant desire for food, resulting in severe obesity. Here we introduce a hereditary familial mutation in leptin receptor gene of two young sisters from a Kurdish-Turkish family who were suffering from severe obesity. Blood samples were taken from all member of the family and DNA was extracted from leukocytes. Sequencing was performed for suspected genes involving in severe obesity. Data analysis showed that two sisters were homozygous for two different missense mutations in the leptin receptor. Their parents were heterozygous for these mutations. Canonical structures Swiss homology modelling of these molecules was prepared. The data suggests that these mutations have impaired the leptin signalling and therefore have caused severe obesity in these two sisters.