De novo 19p13.2 microdeletion encompassing the insulin receptor and resistin genes in a patient with obesity and learning disability

Am J Med Genet A. 2013 Jun;161A(6):1480-6. doi: 10.1002/ajmg.a.35927. Epub 2013 May 1.

Abstract

Genetic studies have provided novel insights of appetite regulation and pathophysiology of obesity. The adipose tissue is an active endocrine organ secreting several hormones contributing to insulin resistance and the development of the comorbidities of obesity, such as type 2 diabetes and cardiovascular disease. Herein, we report on a patient with severe obesity and mild learning disability with a 750 kb de novo deletion of chromosome 19. The deletion encompasses several genes, including resistin and the first part of the insulin receptor, genes that are relevant for obesity. This novel deletion may therefore represent a region for obesity research. Plasma analyses and gene expression demonstrated that the deletion resulted in haploinsufficiency for resistin and insulin receptor in the patient compared to controls. We then studied the biochemical and adipocytokine profile in these subjects. We observed no differences in glucose and lipid parameters between the patient and the controls. Thus, haploinsufficiency of insulin receptor and resistin does not appear to influence glucose and lipid metabolism. However, the patient had considerably higher values of adiponectin and TNFα than controls. In conclusion, we identified a 19p13.2 microdeletion encompassing the insulin receptor and resistin genes resulting in haploinsufficiency in an obese, but otherwise healthy patient. No firm conclusions could be drawn regarding the potential effect of the microdeletion on adipokine profile.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / blood
  • Adiponectin / blood
  • Adult
  • Blood Glucose
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 19 / genetics*
  • Comparative Genomic Hybridization
  • Female
  • Haploinsufficiency
  • Humans
  • Learning Disabilities / genetics*
  • Lipid Metabolism
  • Obesity, Morbid / genetics*
  • Receptor, Insulin / genetics*
  • Resistin / blood
  • Resistin / genetics*
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Adipokines
  • Adiponectin
  • Blood Glucose
  • Resistin
  • Tumor Necrosis Factor-alpha
  • Receptor, Insulin