A de novo mutation affecting human TrkB associated with severe obesity and developmental delay.
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.
Yeo
Giles S H
GS
University Department of Clinical Biochemistry, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge CB2 2XY, UK.
Connie Hung
Chiao-Chien
CC
Rochford
Justin
J
Keogh
Julia
J
Gray
Juliette
J
Sivaramakrishnan
Shoba
S
O'Rahilly
Stephen
S
Farooqi
I Sadaf
IS
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
D019208:Brain-Derived Neurotrophic Factor; D014443:Tyrosine; D020813:Receptor, trkB; D003545:Cysteine