Genetic and Molecular Characterization of Restless Legs Syndrome

不安腿综合征的遗传和分子特征

• 批准号: 7465546
• 负责人: Jacinda Beth Sampson
• 金额: $ 17.88万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7465546
• 关键词: Affect; Age; Aging; Agitation; American; Area; Biopsy; Blood Tests; Brain; Candidate Disease Gene; Chromosome Mapping; Circadian Rhythms; Clinic; Clinical Research; Condition; DNA Library; Data; Databases; Development; Diabetes Mellitus; Diagnostic; Diagnostic Procedure; Disease; Dopamine; Drowsiness; Esthesia; Evaluation; Family; Family Study; Feeling; Fiber; Genes; Genome; Goals; Home environment; Human Genome Project; Hypothyroidism; Immobilization; Incidence; Inheritance Patterns; Inherited; Interview; Iron; Kidney Failure; Leg; Life; Measures; Medical; Microsatellite Repeats; Modeling; Molecular Genetics; Movement; Mutation; Neurodegenerative Disorders; Neurologic; Neurologic Examination; Neuropathy; Parkinson Disease; Participant; Pathway interactions; Penetrance; Peripheral Nervous System Diseases; Persons; Pharmaceutical Preparations; Phenotype; Population; Productivity; Proteins; Protocols documentation; Quality of life; Questionnaires; Recording of previous events; Reporting; Research Ethics Committees; Research Personnel; Rest; Restless Legs Syndrome; Sampling; Secondary to; Sensitivity and Specificity; Single Nucleotide Polymorphism; Skin; Sleep; Standards of Weights and Measures; Surveys; Symptoms; Syndrome; Techniques; Testing; Universities; Utah; Work; affection; base; genetic linkage analysis; genetic pedigree; improved; kindred; nervous system disorder; neurochemistry; programs

DESCRIPTION (provided by applicant): The goal of this project is to find and characterize the gene or genes responsible for familial restless legs syndrome (RLS). Restless legs syndrome is a common disorder, affecting up to 10-15% of the population, and is frequently inherited. RLS consists of an uncomfortable feeling in the legs, occurring at rest, which worsens in the evenings and is partially relieved by movement. Several large Utah families with RLS have participated in our previous preliminary studies to date. We propose to differentiate between inherited RLS and RLS secondary to several common medical illnesses by a thorough history and neurological exam, commonly available blood tests to exclude those medical conditions, and a Suggested Immobilization Test (SIT). The SIT test has been shown to be both sensitive and specific for the RLS syndrome. We then plan to perform linkage analysis on the banked DNA, identify candidate genes from the promising regions using the Human Genome Project database, and screen for causative mutations in these candidate genes. RLS symptoms are often relieved by dopaminergic medications. Finding the genes involved in RLS may enlighten us about the neurochemistry of other disorders involving dopamine, including Parkinson's disease. Storage of iron in the brains of persons with RLS is lower than unaffected people, suggesting an interconnection between development of iron stores, dopamine pathways and RLS symptoms. RLS incidence increases with age, but is not a neurodegenerative disorder. Understanding RLS may improve our understanding of brain maturation and aging, and circadian rhythms. RLS affects about 1 in 10 people, and becomes more common with increasing age. It can be caused by several common medical conditions, but is frequently inherited. Persons with RLS often pace at night to relieve their symptoms, suffer from lack of sleep, and are sleepy during the daytime due to RLS. This adversely affects their productivity at work and their quality of life at home.

描述（由申请人提供）：该项目的目标是寻找并表征导致家族性不宁腿综合症（RLS）的一个或多个基因。不宁腿综合症是一种常见疾病，影响高达 10-15% 的人口，并且通常具有遗传性。不宁腿综合征是指休息时腿部出现不舒服的感觉，这种感觉在晚上会加重，运动后可部分缓解。迄今为止，犹他州的几个患有不宁腿综合症的大家庭已经参与了我们之前的初步研究。我们建议通过全面的病史和神经系统检查、排除这些疾病的常用血液检查以及建议的制动测试 (SIT) 来区分遗传性不宁腿综合症和继发于几种常见疾病的不宁腿综合症。 SIT 测试已被证明对 RLS 综合征既敏感又特异。然后，我们计划对库存的 DNA 进行连锁分析，使用人类基因组计划数据库从有希望的区域中识别候选基因，并筛选这些候选基因中的致病突变。 RLS 症状通常可通过多巴胺能药物缓解。找到与不宁腿综合征有关的基因可能会启发我们了解其他涉及多巴胺的疾病（包括帕金森病）的神经化学。患有不宁腿综合症的人大脑中铁的储存量低于未受影响的人，这表明铁储存的发展、多巴胺通路和不宁腿综合症症状之间存在相互关联。 RLS 发病率随着年龄的增长而增加，但不是一种神经退行性疾病。了解 RLS 可以提高我们对大脑成熟和衰老以及昼夜节律的理解。不宁腿综合症影响大约十分之一的人，并且随着年龄的增长而变得更加常见。它可能是由几种常见的医疗状况引起的，但通常是遗传性的。患有不宁腿综合症的人经常在夜间踱步以缓解症状，导致睡眠不足，并且由于不宁腿综合症而在白天感到困倦。这会对他们的工作效率和家庭生活质量产生不利影响。