PMID- 17130481
OWN - NLM
STAT- MEDLINE
DCOM- 20070116
LR  - 20220408
IS  - 0012-1797 (Print)
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Linking)
VI  - 55
IP  - 12
DP  - 2006 Dec
TI  - Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity 
      associated with functional loss of one copy of the brain-derived neurotrophic 
      factor (BDNF) gene.
PG  - 3366-71
AB  - 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.
FAU - Gray, Juliette
AU  - Gray J
AD  - University Department of Clinical Biochemistry, Cambridge Institute for Medical 
      Research, Addenbrooke's Hospital, Cambridge, CB2 2XY, U.K.
FAU - Yeo, Giles S H
AU  - Yeo GS
FAU - Cox, James J
AU  - Cox JJ
FAU - Morton, Jenny
AU  - Morton J
FAU - Adlam, Anna-Lynne R
AU  - Adlam AL
FAU - Keogh, Julia M
AU  - Keogh JM
FAU - Yanovski, Jack A
AU  - Yanovski JA
FAU - El Gharbawy, Areeg
AU  - El Gharbawy A
FAU - Han, Joan C
AU  - Han JC
FAU - Tung, Y C Loraine
AU  - Tung YC
FAU - Hodges, John R
AU  - Hodges JR
FAU - Raymond, F Lucy
AU  - Raymond FL
FAU - O'rahilly, Stephen
AU  - O'rahilly S
FAU - Farooqi, I Sadaf
AU  - Farooqi IS
LA  - eng
GR  - Z01 HD000641/ImNIH/Intramural NIH HHS/United States
GR  - Z99 HD999999/ImNIH/Intramural NIH HHS/United States
GR  - 068086/WT_/Wellcome Trust/United Kingdom
GR  - G9824984/MRC_/Medical Research Council/United Kingdom
GR  - G9724461/MRC_/Medical Research Council/United Kingdom
GR  - Z01 HD000641-12/ImNIH/Intramural NIH HHS/United States
GR  - MC_U105559861/MRC_/Medical Research Council/United Kingdom
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adult
MH  - Brain-Derived Neurotrophic Factor/blood/*genetics
MH  - *Chromosome Aberrations
MH  - Chromosome Inversion/*genetics
MH  - Chromosomes, Artificial, Bacterial
MH  - Cognition Disorders/*genetics
MH  - DNA/genetics/isolation & purification
MH  - Female
MH  - Humans
MH  - Hyperkinesis/*genetics
MH  - Hyperphagia/*genetics
MH  - *Mutation
MH  - Obesity/*genetics
PMC - PMC2413291
MID - NIHMS51342
EDAT- 2006/11/30 09:00
MHDA- 2007/01/17 09:00
PMCR- 2008/06/05
CRDT- 2006/11/30 09:00
PHST- 2006/11/30 09:00 [pubmed]
PHST- 2007/01/17 09:00 [medline]
PHST- 2006/11/30 09:00 [entrez]
PHST- 2008/06/05 00:00 [pmc-release]
AID - 55/12/3366 [pii]
AID - 10.2337/db06-0550 [doi]
PST - ppublish
SO  - Diabetes. 2006 Dec;55(12):3366-71. doi: 10.2337/db06-0550.