WAGR Syndrome and Other 11p Contiguous Gene Deletions: Clinical Characterization and Correlation With Genotype
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 197
- 试验地点
- 1
研究概览
简要总结
This study will explore conditions caused by the absence of certain genes on chromosome 11. These conditions include WAGR syndrome, which is characterized by a kidney tumor called Wilm s tumor, aniridia (absence of the iris of the eye), genital and urinary abnormalities, mental retardation, and possibly other symptoms. This study will examine how the genes on chromosome 11 affect people and whether the absence of specific genes is associated with specific symptoms.
Healthy normal volunteers, people with isolated aniridia, and people with WAGR or another chromosome 11 gene deletion may be eligible for this study. Participants must be at least 6 years old. Parents of patients may also participate for genetic studies.
Participants undergo some or all of the following procedures, depending on whether they are a child, adult, healthy volunteer or parent of a patient:
- Medical history and physical examination, eye examination, blood, urine and saliva tests, electrocardiogram (EKG) and electroencephalogram (EEG)
- X-rays, scans and other tests to measure body composition (fat, muscle and bone development and thickness) and MRI to examine the eyes and the brain and to measure abdominal fat
- Ultrasound studies of the kidneys, ovaries and uterus (in females) and testes (in males)
- Meal tests, food diaries and food preference tests
- Questionnaires about eating and sleep habits, personality and character traits and responses to pain and injury
- Neuropsychological tests
- Tests of resting metabolic rate, energy expenditure and glucose (sugar) tolerance
- Hot and cold sensitivity tests, vibration sensitivity test, cold tolerance test and smell identification test
- Eye and hearing tests
- Nerve conduction studies and study of sensory information conduction from peripheral nerves to the spinal cord and brain
- Computer photography
- Evaluation by sub-specialists (e.g., endocrinologist, ophthalmologist, physiatrist, neurologist or others) as indicated by the patient s medical history and test results
详细描述
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.
研究设计
- 研究类型
- Observational
- 时间视角
- Other
入排标准
- 年龄范围
- 2 Years 至 99 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供