WAGR Syndrome and Other 11p Contiguous Gene Deletions: Clinical Characterization and Correlation With Genotype
WAGR syndrome is a rare genetic disorder characterized by Wilms tumor, aniridia,
genitourinary anomalies and mental retardation. The syndrome is caused by heterozygous
contiguous gene deletions of variable size on chromosome 11, involving a region that
encompasses more than 100 genes, many of which have unknown function in humans. In our
preliminary studies, we have observed that approximately two-thirds of patients with WAGR
syndrome have deletion of the gene which encodes brain-derived neurotrophic factor (BDNF),
and that BDNF haploinsufficiency is associated with obesity and with parent reports of
hyperphagia and impaired nociception, suggesting that BDNF may play an important role in
human energy balance as well as pain sensation. We now propose to conduct a comprehensive
clinical phenotype-genotype study on patients with WAGR syndrome and other 11p deletions. We
plan to enroll 75 subjects with WAGR syndrome/11p deletions who will undergo evaluations of
the following systems: metabolic/endocrine, sensation/nociception, ophthalmologic,
audiologic, neurocognitive, renal/genitourinary, oncologic, dental/craniofacial, cardiac,
and orthopedic. Genetic testing will be performed on the parents of subjects with WAGR
syndrome/11p deletion who choose to participate in order to determine if parental origin of
the deletion influences phenotype. We also plan to enroll 75 healthy subjects as body-size
matched controls for metabolic studies and 75 patients with isolated aniridia as visually
impaired controls for neurocognitive studies. We hypothesize that a more complete
understanding of the correlation between phenotype and genotype could lead to improved
medical care of these patients through genotype-specific management as well as yield further
insight into the physiological role of genes in the 11p region.
Observational
N/A
Joan C Han, M.D.
Principal Investigator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
United States: Federal Government
080213
NCT00758108
September 2008
Name | Location |
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National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda, Maryland 20892 |