Prevalence of FMRI Expansions in Movement Disorders

描述（由申请人提供）：Deborah Ann Hall博士正在申请运动障碍领域的pented患者导向研究（K23）奖。本提案描述了神经病学临床研究者发展的研究和培训计划。首席研究员霍尔博士完成了神经内科住院医师培训和运动障碍奖学金。她获得了美国神经病学学会的竞争性临床研究奖学金，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相关的震颤/共济失调综合征。她的长期目标是研究共济失调的遗传危险因素、神经流行病学和治疗，包括散发性共济失调。在获奖期间，Hall博士将在科罗拉多大学（UCDHSC）神经内科工作。UCDHSC在支持和发展临床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多学科临床研究。该候选人将与Tim Byers医学博士（流行病学）、Maureen Leehey医学博士（神经病学）、Gary Zerbe博士（生物统计学）和Paul Hagerman医学博士（生物化学）一起进行研究。Hall博士的研究项目是确定震颤、共济失调和/或帕金森患者中FMR1（脆性X智力迟钝）基因重复扩增的流行程度。霍尔博士将通过在她的诊所招募具有三种表型的受试者并对FMR1基因进行PCR来进行横断面研究。所有符合条件的受试者将被招募，基因检测将在研究实验室进行。要测量的主要结果是三组和每个表型亚组中重复扩增的发生率。发病年龄、神经症状诊断年龄以及三核苷酸重复序列大小与表型之间的相关性也是需要测量的结果。将使用线性和逻辑回归模型，并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，因为它可以确定各种异常运动（如震颤）的遗传风险因素。这将改善对进行性神经疾病患者的诊断和潜在治疗。这些疾病代表了一个重要的公共卫生问题，因为它们在我们的老龄化人口中导致发病率和死亡率。

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.