Prevalence of FMRI Expansions in Movement Disorders

描述(由申请者提供)：黛博拉·安·霍尔博士正在申请运动障碍领域的五项以患者为导向的研究(K23)奖。这项建议描述了一项研究和培训计划，以发展神经病学的临床医生-研究员。首席研究员霍尔博士已经完成了神经学住院医师培训，并获得了运动障碍奖学金。她获得了美国神经病学学会颁发的竞争性临床研究奖学金，目前正在攻读临床科学博士学位。候选人的近期目标是通过在拟议的项目中直接应用她新获得的流行病学和生物统计学技能，继续研究脆性X相关震颤/共济失调综合症。她的长期目标是研究共济失调的遗传风险因素、神经流行病学和治疗，包括散发性共济失调。在获奖期间，霍尔博士将常驻科罗拉多大学(UCDHSC)神经病学系。UCDHSC在支持和发展临床医生-研究人员方面有着广泛的记录。UCDHSC的临床科学博士项目促进了有指导的多学科临床研究。候选人将与蒂姆·拜尔斯博士(流行病学)、莫琳·利希博士(神经学)、加里·泽贝博士(生物统计学)和保罗·哈格曼博士(生物化学)进行她的研究。霍尔博士的研究计划是确定FMR1(脆性X智力低下)基因在震颤、共济失调和/或帕金森症患者中重复扩增的发生率。霍尔博士将进行一项横断面研究，在她的诊所招募具有这三种表型的受试者，并对FMR1基因进行聚合酶链式反应。所有符合条件的受试者都将被招募，基因测试将在研究实验室进行。要测量的主要结果是三组合并和每个表型亚组中重复扩张的流行率。发病年龄、神经体征的诊断年龄以及三核苷酸重复大小和表型之间的相关性也是需要测量的结果。将使用线性和Logistic回归模型，并将研究包括种族和民族在内的协变量。相关性：这项研究很重要，因为它可能确定各种异常运动的遗传风险因素，如震颤。这将改善对患有进行性神经系统疾病的个人的诊断和潜在的治疗。这些疾病是一个重要的公共卫生问题，因为它们导致我们老龄化人口的发病率和死亡率。

DESCRIPTION (provided by applicant): Dr. Deborah Ann Hall is applying for a Pentored Patient-Oriented Research (K23) Award in the area of movement disorders. This proposal describes a research and training program for the development of a clinician-investigator in neurology. The principal investigator, Dr. Hall, has completed neurology residency training and a movement disorders fellowship. She received a competitive clinical research fellowship from the American Academy of Neurology and is pursuing a Ph.D. in Clinical Science. The candidate's immediate goals are to continue research in the fragile X-associated tremor/ataxia syndrome, by directly applying her newly acquired epidemiologic and biostatistics skills in the proposed project. Her long term goals are to study the genetic risk factors, neuroepidemiology and treatment of ataxia, including sporadic ataxia. During the award period, Dr. Hall will be based in the Department of Neurology at the University of Colorado (UCDHSC). UCDHSC has an extensive track record for supporting and developing clinician-investigators. The Ph.D. in Clinical Sciences program at UCDHSC facilitates mentored multidisciplinary clinical research. The candidate will carry out her research with Professors Tim Byers MD (Epidemiology), Maureen Leehey MD (Neurology), Gary Zerbe PhD (Biostatistics), and Paul Hagerman MD PhD (Biological Chemistry). Dr. Hall's research program is to determine the prevalence of repeat expansions in the FMR1 (fragile X mental retardation) gene in subjects with tremor, ataxia and/or parkinsonism. Dr. Hall will do a cross-sectional study by recruiting subjects in her clinics with the three phenotypes and performing PCR of the FMR1 gene. All subjects eligible will be recruited and the genetic testing will be done in a research laboratory. The primary outcomes to be measured are the prevalence of repeat expansions in the three groups combined and each phenotypic subgroup. The age of onset, age of diagnosis of neurological signs and correlations between tri-nucleotide repeat size and phenotype are also outcomes to be measured. Linear and logistic regression models will be used and covariates including race and ethnicity will be studied. Relevance: This study is important because it may define genetic risk factors for various abnormal movements, such as tremor. This will result in improved diagnosis and potentially treatment of individuals with progressive neurological diseases. These illnesses represent an important public health problem as they cause morbidity and mortality in our aging population.