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: 7251597
• 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/7251597
• 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）：该项目的目的是查找和表征负责家族不安腿综合征（RLS）的基因或基因。不安的腿综合症是一种常见的疾病，影响多达10-15％的人口，并且经常被遗传。 RLS由腿部的一种不舒服的感觉组成，发生在静止状态，在晚上恶化，并因运动而部分缓解。迄今为止，有几个具有RLS的大型犹他州家庭已经参加了我们以前的初步研究。我们建议通过彻底的病史和神经检查，将遗传的RLS和继发于几种常见医学疾病的RLS区分，通常可用的血液检查以排除这些医疗状况，以及建议的固定测试（SIT）。 SIT测试已被证明对RLS综合征既敏感又具有特异性。然后，我们计划对银行DNA进行连锁分析，使用人类基因组项目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。多巴胺能药物通常可以缓解RLS症状。发现RLS涉及的基因可能会启发我们有关涉及多巴胺的其他疾病的神经化学，包括帕金森氏病。 RLS患者的大脑中铁的存储低于未受影响的人，这表明铁储存，多巴胺途径和RLS症状之间存在相互联系。 RLS发病率随着年龄的增长而增加，但不是神经退行性疾病。了解RLS可以提高我们对大脑成熟和衰老的理解，以及昼夜节律。 RLS影响大约十分之一的人，并且随着年龄的增长而变得更加普遍。它可能是由几种常见的医疗状况引起的，但经常是继承的。患有RLS的人经常在晚上速度缓解症状，缺乏睡眠，并且由于RLS而在白天昏昏欲睡。这不利地影响了他们在工作中的生产力和在家中的生活质量。