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BDNF Haploinsufficiency in Patients with WAGR Syndrome
Is Associated with Decreased Behavioral Responses to Pain
Rebecca L. Levinn, Jack W. Tsao, Diane C. Adler-Wailes, Chanelle A. Wijesinghe, Kyra S. Jefferson-George, Owen M. Rennert, Jack A. Yanovski, Joan C. Han. Unit on Growth and Obesity, PDEGEN, NICHD, National Institutes of Health, Bethesda, MD; Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD.
BACKGROUND: WAGR syndrome (Wilms tumor, Aniridia, Genitourinary abnormalities, and mental Retardation) is caused by heterozygous contiguous gene deletions of variable size on Chromosome 11. The gene that encodes brain-derived neurotrophic factor (BDNF) is included in the region of deletion in about half of WAGR patients. In animal studies, BDNF appears to play a role in modulating nociceptive sensory inputs. No quantitative data exist relating pain perception to BDNF haploinsufficiency in humans.
OBJECTIVE: To study patients with WAGR syndrome to determine if parent-reported behavioral responses to pain differ among those with and without BDNF haploinsufficiency.
DESIGN/METHODS: Comparative genomic hybridization was performed for 31 subjects with WAGR syndrome (age 13.9 8.3y) to establish if one copy of the BDNF gene was deleted. Parents completed the Non-Communicating Children s Pain Checklist-Revised (NCCPC-R), which assesses occurrence of behavioral responses (subscales: vocal, social, facial, physical activity, body and limb, physiological, and eating/sleeping) to injuries and illnesses considered painful to most people. Scores for subjects with and without BDNF haploinsufficiency were compared using the Mann-Whitney U test.
RESULTS: 58% of subjects had BDNF haploinsufficiency (BDNF+/-). Compared to those with both BDNF alleles intact (BDNF+/+), BDNF+/- subjects had lower mean NCCPC-R total response scores (BDNF+/- vs. BDNF+/+: 22.815.9 vs. 35.417.0, p=0.031), as well as lower NCCPC-R subscores for vocal (p=0.010), facial (p=0.043), body and limb (p=0.033), and physiological (p=0.044) responses (primarily subscales that reflect perception of pain intensity). No statistically significant differences were observed for social, physical activity, and eating/sleeping responses (subscales previously found not to be correlated with pain intensity).
CONCLUSIONS: Among individuals with WAGR syndrome, BDNF haploinsufficiency is associated with fewer behavioral responses to typically painful stimuli. These data support a role for BDNF in human nociception.
First Author is a Student
E-PAS2008:634504.8
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