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

• Published in: American journal of medical genetics. Part A Vol. 161A; no. 6; pp. 1480 - 1486
• Main Authors: Wangensteen, Teresia, Retterstøl, Lars, Rødningen, Olaug K., Hjelmesæth, Jøran, Aukrust, Pål, Halvorsen, Bente
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.06.2013; Wiley Subscription Services, Inc
• Subjects: 19p13.2; Adipokines - blood; Adiponectin; Adiponectin - blood; Adult; Blood Glucose; Chromosome Deletion; Chromosomes, Human, Pair 19 - genetics; Comparative Genomic Hybridization; Female; Haploinsufficiency; Humans; insulin receptor; Learning Disorders - genetics; Lipid Metabolism; microdeletion; obesity; Obesity, Morbid - genetics; Receptor, Insulin - genetics; resistin; Resistin - blood; Resistin - genetics; Tumor Necrosis Factor-alpha - blood
• ISSN: 1552-4825; 1552-4833; 1552-4833
• DOI: 10.1002/ajmg.a.35927

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. © 2013 Wiley Periodicals, Inc.