PMID- 23517654
OWN - NLM
STAT- MEDLINE
DCOM- 20140730
LR  - 20211021
IS  - 1973-8102 (Electronic)
IS  - 0010-9452 (Print)
IS  - 0010-9452 (Linking)
VI  - 49
IP  - 10
DP  - 2013 Nov-Dec
TI  - Association of brain-derived neurotrophic factor (BDNF) haploinsufficiency with 
      lower adaptive behaviour and reduced cognitive functioning in WAGR/11p13 deletion 
      syndrome.
PG  - 2700-10
LID - S0010-9452(13)00047-6 [pii]
LID - 10.1016/j.cortex.2013.02.009 [doi]
AB  - In animal studies, brain-derived neurotrophic factor (BDNF) is an important 
      regulator of central nervous system development and synaptic plasticity. WAGR 
      (Wilms tumour, Aniridia, Genitourinary anomalies, and mental Retardation) 
      syndrome is caused by 11p13 deletions of variable size near the BDNF locus and 
      can serve as a model for studying human BDNF haploinsufficiency (+/-). We 
      hypothesized that BDNF+/- would be associated with more severe cognitive 
      impairment in subjects with WAGR syndrome. Twenty-eight subjects with WAGR 
      syndrome (6-28 years), 12 subjects with isolated aniridia due to PAX6 
      mutations/microdeletions (7-54 years), and 20 healthy controls (4-32 years) 
      received neurocognitive assessments. Deletion boundaries for the subjects in the 
      WAGR group were determined by high-resolution oligonucleotide array comparative 
      genomic hybridization. Within the WAGR group, BDNF+/- subjects (n = 15), compared 
      with BDNF intact (+/+) subjects (n = 13), had lower adaptive behaviour (p = .02), 
      reduced cognitive functioning (p = .04), higher levels of reported historical (p 
      = .02) and current (p = .02) social impairment, and higher percentage meeting 
      cut-off score for autism (p = .047) on Autism Diagnostic Interview-Revised. These 
      differences remained nominally significant after adjusting for visual acuity. 
      Using diagnostic measures and clinical judgement, 3 subjects (2 BDNF+/- and 1 
      BDNF+/+) in the WAGR group (10.7%) were classified with autism spectrum disorder. 
      A comparison group of visually impaired subjects with isolated aniridia had 
      cognitive functioning comparable to that of healthy controls. In summary, among 
      subjects with WAGR syndrome, BDNF+/- subjects had a mean Vineland Adaptive 
      Behaviour Compose score that was 14-points lower and a mean intelligence quotient 
      (IQ) that was 20-points lower than BDNF+/+ subjects. Our findings support the 
      hypothesis that BDNF plays an important role in human neurocognitive development.
CI  - Published by Elsevier Ltd.
FAU - Han, Joan C
AU  - Han JC
AD  - Unit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National 
      Institute of Child Health and Human Development (NICHD), National Institutes of 
      Health, Bethesda, MD, USA; Section on Growth and Obesity, Program in 
      Developmental Endocrinology and Genetics, NICHD, National Institutes of Health, 
      Bethesda, MD, USA. Electronic address: hanjo@mail.nih.gov.
FAU - Thurm, Audrey
AU  - Thurm A
FAU - Golden Williams, Christine
AU  - Golden Williams C
FAU - Joseph, Lisa A
AU  - Joseph LA
FAU - Zein, Wadih M
AU  - Zein WM
FAU - Brooks, Brian P
AU  - Brooks BP
FAU - Butman, John A
AU  - Butman JA
FAU - Brady, Sheila M
AU  - Brady SM
FAU - Fuhr, Shannon R
AU  - Fuhr SR
FAU - Hicks, Melanie D
AU  - Hicks MD
FAU - Huey, Amanda E
AU  - Huey AE
FAU - Hanish, Alyson E
AU  - Hanish AE
FAU - Danley, Kristen M
AU  - Danley KM
FAU - Raygada, Margarita J
AU  - Raygada MJ
FAU - Rennert, Owen M
AU  - Rennert OM
FAU - Martinowich, Keri
AU  - Martinowich K
FAU - Sharp, Stephen J
AU  - Sharp SJ
FAU - Tsao, Jack W
AU  - Tsao JW
FAU - Swedo, Susan E
AU  - Swedo SE
LA  - eng
GR  - Z01 HD000641/Intramural NIH HHS/United States
GR  - ZIAHD008898/PHS HHS/United States
GR  - Z1AHD00641/PHS HHS/United States
GR  - ZIAMH002868/PHS HHS/United States
GR  - ZIA MH002868/Intramural NIH HHS/United States
GR  - ZIA HD008898/Intramural NIH HHS/United States
GR  - Z99 HD999999/Intramural NIH HHS/United States
GR  - ZIA HD008898-03/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20130219
PL  - Italy
TA  - Cortex
JT  - Cortex; a journal devoted to the study of the nervous system and behavior
JID - 0100725
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - Chromosome 11p, partial deletion
SB  - IM
MH  - Adaptation, Psychological/*physiology
MH  - Adolescent
MH  - Adult
MH  - Aniridia/complications/genetics
MH  - Autistic Disorder/genetics/psychology
MH  - Behavior/physiology
MH  - Brain/pathology
MH  - Brain-Derived Neurotrophic Factor/*deficiency
MH  - Child
MH  - Child Behavior Disorders/etiology/psychology
MH  - Child, Preschool
MH  - Chromosome Deletion
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 11/genetics
MH  - Cognition/physiology
MH  - Cognition Disorders/*genetics/physiopathology/*psychology
MH  - Cohort Studies
MH  - Corpus Callosum/pathology
MH  - Female
MH  - Haploinsufficiency/*genetics/*physiology
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - Neuropsychological Tests
MH  - Vision Tests
MH  - Visual Acuity
MH  - WAGR Syndrome/*genetics
MH  - Young Adult
PMC - PMC3762943
MID - NIHMS462248
OTO - NOTNLM
OT  - 11p Deletion
OT  - Autism
OT  - Brain-derived neurotrophic factor
OT  - IQ
OT  - WAGR syndrome
EDAT- 2013/03/23 06:00
MHDA- 2014/07/31 06:00
PMCR- 2014/11/01
CRDT- 2013/03/23 06:00
PHST- 2012/11/15 00:00 [received]
PHST- 2013/02/08 00:00 [revised]
PHST- 2013/02/11 00:00 [accepted]
PHST- 2013/03/23 06:00 [entrez]
PHST- 2013/03/23 06:00 [pubmed]
PHST- 2014/07/31 06:00 [medline]
PHST- 2014/11/01 00:00 [pmc-release]
AID - S0010-9452(13)00047-6 [pii]
AID - 10.1016/j.cortex.2013.02.009 [doi]
PST - ppublish
SO  - Cortex. 2013 Nov-Dec;49(10):2700-10. doi: 10.1016/j.cortex.2013.02.009. Epub 2013 
      Feb 19.