Hyperphagia, Severe Obesity, Impaired Cognitive Function, and Hyperactivity Associated With Functional Loss of One Copy of the Brain-Derived Neurotrophic Factor (BDNF) Gene
- 1 December 2006
- journal article
- case report
- Published by American Diabetes Association in Diabetes
- Vol. 55 (12), 3366-3371
- https://doi.org/10.2337/db06-0550
Abstract
The neurotrophin brain-derived neurotrophic factor (BDNF) inhibits food intake, and rodent models of BDNF disruption all exhibit increased food intake and obesity, as well as hyperactivity. We report an 8-year-old girl with hyperphagia and severe obesity, impaired cognitive function, and hyperactivity who harbored a de novo chromosomal inversion, 46,XX,inv(11)(p13p15.3), a region encompassing the BDNF gene. We have identified the proximal inversion breakpoint that lies 850 kb telomeric of the 5′ end of the BDNF gene. The patient’s genomic DNA was heterozygous for a common coding polymorphism in BDNF, but monoallelic expression was seen in peripheral lymphocytes. Serum concentration of BDNF protein was reduced compared with age- and BMI-matched subjects. Haploinsufficiency for BDNF was associated with increased ad libitum food intake, severe early-onset obesity, hyperactivity, and cognitive impairment. These findings provide direct evidence for the role of the neurotrophin BDNF in human energy homeostasis, as well as in cognitive function, memory, and behavior.This publication has 27 references indexed in Scilit:
- Serum Brain-Derived Neurotrophic Factor Concentrations in Lean and Overweight Children and AdolescentsJournal of Clinical Endocrinology & Metabolism, 2006
- Neurogenesis in the Hypothalamus of Adult Mice: Potential Role in Energy BalanceScience, 2005
- BDNF function in adult synaptic plasticity: The synaptic consolidation hypothesisProgress in Neurobiology, 2005
- Anatomy and regulation of the central melanocortin systemNature Neuroscience, 2005
- Monogenic Obesity in HumansAnnual Review of Medicine, 2005
- Physiology of BDNF: focus on hypothalamic functionFrontiers in Neuroendocrinology, 2004
- The BDNF val66met Polymorphism Affects Activity-Dependent Secretion of BDNF and Human Memory and Hippocampal FunctionCell, 2003
- Conditional Deletion Of Brain-Derived Neurotrophic Factor in the Postnatal Brain Leads to Obesity and HyperactivityMolecular Endocrinology, 2001
- Characteristics of BDNF-induced weight lossExperimental Neurology, 1995
- Functions of the neurotrophins during nervous system development: What the knockouts are teaching usCell, 1994