Journal of Isfahan Medical School

Journal of Isfahan Medical School

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

Document Type : Original Article(s)

Authors
Arash Babaei 1
Seyed Jamal Moshtaghian 2
1 Assistant Professor, Departmen of Giology, School of Scisnse, The University of Malayer, Malayer, Iran
2 Assistant Professor, Departmen of Giology, School of Scisnse, The University of Isfahan, Isfahan, Iran
Abstract
Introduction: Obesity, a growing universal problem, is a disorder/illness related to several factors. These factors includ 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.Methods: 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. Canonical structures Swiss homology modelling of these molecules was prepared.Finding: Data analysis showed that two sisters were homozygous for two different missense mutations in the leptin receptor. Their parents were heterozygous for these mutations.Conclusion: The data suggests that these mutations have impaired the leptin signalling and therefore have caused severe obesity in these two sisters.
Keywords
Severe obesity
Homozygous Missense mutations
Leptin receptor
Swiss homology modelling
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Journal of Isfahan Medical School
Volume 28, Issue 121 - Serial Number 121
November and December 2011
Pages 1606-1616

  • Receive Date 27 February 2011
  • Accept Date 06 April 2022