title: A de novo mutation affecting human TrkB associated with severe obesity and developmental delay.
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.
authors.affiliation: University Department of Clinical Biochemistry, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge CB2 2XY, UK.
authors.forename: Giles S H
authors.initials: GS
authors.lastname: Yeo
authors.forename: Chiao-Chien
authors.initials: CC
authors.lastname: Connie Hung
authors.forename: Justin
authors.initials: J
authors.lastname: Rochford
authors.forename: Julia
authors.initials: J
authors.lastname: Keogh
authors.forename: Juliette
authors.initials: J
authors.lastname: Gray
authors.forename: Shoba
authors.initials: S
authors.lastname: Sivaramakrishnan
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Rahilly
authors.forename: I Sadaf
authors.initials: IS
authors.lastname: Farooqi
mesh_terms: D000367:Age Factors; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D019556:COS Cells / Q000378:metabolism; D002648:Child; D003545:Cysteine / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D002658:Developmental Disabilities / Q000150:complications / Q000235:genetics*; D004435:Eating; D005455:Fluorescent Antibody Technique / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000235:genetics; D020125:Mutation, Missense; D009765:Obesity / Q000150:complications / Q000235:genetics*; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D020813:Receptor, trkB / Q000235:genetics*; D014162:Transfection / Q000379:methods; D014443:Tyrosine / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D014443:Tyrosine; D020813:Receptor, trkB; D003545:Cysteine