A de novo mutation affecting human TrkB associated with severe obesity and developmental delay

Nat Neurosci. 2004 Nov;7(11):1187-9. doi: 10.1038/nn1336. Epub 2004 Oct 24.

Abstract

An 8-year-old male with a complex developmental syndrome and severe obesity was heterozygous for a de novo missense mutation resulting in a Y722C substitution in the neurotrophin receptor TrkB. This mutation markedly impaired receptor autophosphorylation and signaling to MAP kinase. Mutation of NTRK2, which encodes TrkB, seems to result in a unique human syndrome of hyperphagic obesity. The associated impairment in memory, learning and nociception seen in the proband reflects the crucial role of TrkB in the human nervous system.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Blotting, Western / methods
  • Body Mass Index
  • Body Weight / genetics
  • Brain-Derived Neurotrophic Factor / pharmacology
  • COS Cells / metabolism
  • Child
  • Cysteine / genetics
  • DNA Mutational Analysis / methods
  • Developmental Disabilities / complications
  • Developmental Disabilities / genetics*
  • Eating
  • Fluorescent Antibody Technique / methods
  • Gene Expression Regulation / drug effects
  • Humans
  • MAP Kinase Signaling System / genetics
  • Male
  • Memory Disorders / etiology
  • Memory Disorders / genetics
  • Mutation, Missense*
  • Obesity / complications
  • Obesity / genetics*
  • PC12 Cells / drug effects
  • PC12 Cells / metabolism
  • Phosphorylation
  • Rats
  • Receptor, trkB / genetics*
  • Transfection / methods
  • Tyrosine / genetics

Substances

  • Brain-Derived Neurotrophic Factor
  • Tyrosine
  • Receptor, trkB
  • Cysteine