Cognitive Genetic Aspects of Duchenne Muscular Dystrophy

杜氏肌营养不良症的认知遗传方面

• 批准号: 7100088
• 负责人: VERONICA J HINTON
• 金额: $ 37.92万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-05-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7100088
• 关键词: Cognitive; Genetic; Aspects; Duchenne; Muscular

DESCRIPTION (provided by investigator): The objective of this study is to investigate neuropsychological function in individuals diagnosed with Duchenne muscular dystrophy (DMD) as a model for developmental neuroscience. DMD is a single-gene disorder that interferes with the expression of the protein dystrophin and its isoforms. The consequences of lack of dystrophin in muscle are well known; boys have progressive muscular weakness that results in death generally by their third decade of life. Dystrophin isoforms are also missing from the central nervous system, yet what functional consequences that may have is unclear. Interdisciplinary study of the cognitive profile, the behavioral attributes, and the molecular genetics of DMD will examine genotype/phenotype associations. The study will build on work that ascertained neuropsychological function in a group of 136 boys diagnosed with DMD and was completed during the tenure of an R29 award. Those data confirmed that boys with DMD who are of average intelligence have selective deficits in verbal working memory with intact declarative memory and visuospatial skills, poor social skills and delayed language developmental milestones. Selected subjects from the established cohort will be examined more thoroughly in focused paradigms to tease apart their language and short-term memory skills using a battery of tests designed to examine the hypothetical "phonological loop." Additionally, subjects will be tested on measures of social function and awareness. New subjects will also be enrolled to increase our sample size for genetic analyses. Subjects with more mild manifestations of the disorder (boys with Becker's muscular dystrophy and carrier females) will be tested on neuropsychological measures to determine whether they present with cognitive phenotypes. An ongoing longitudinal study of a sample of 26 boys will be continued with neuropsychological testing every other year. And newly characterized preschool boys with DMD will be followed to track their language and emotional development.

描述（由研究者提供）：本研究的目的是研究作为发育神经科学模型的杜氏肌营养不良症（DMD）患者的神经心理功能。DMD是一种单基因疾病，干扰蛋白质肌营养不良蛋白及其亚型的表达。肌肉中缺乏抗肌萎缩蛋白的后果是众所周知的;男孩患有进行性肌无力，通常在他们生命的第三个十年死亡。中枢神经系统中也缺少肌营养不良蛋白亚型，但其可能产生的功能后果尚不清楚。对DMD的认知特征、行为特征和分子遗传学的跨学科研究将检查基因型/表型关联。这项研究将建立在确定一组136名被诊断患有DMD的男孩的神经心理功能的基础上，并在R29奖的任期内完成。这些数据证实，智力一般的DMD男孩在言语工作记忆方面存在选择性缺陷，陈述性记忆和视觉空间技能完整，社交技能差，语言发育里程碑延迟。从已建立的队列中选择的受试者将在集中的范式中进行更彻底的检查，以使用一组旨在检查假设的“语音回路”的测试来梳理他们的语言和短期记忆技能。“此外，受试者将接受社会功能和意识的测试。还将招募新受试者，以增加我们用于遗传分析的样本量。将对具有更轻微的疾病表现的受试者（患有贝克尔肌营养不良症的男孩和携带者女性）进行神经心理学测量以确定他们是否存在认知表型。一项对26名男孩进行的纵向研究将每隔一年进行一次神经心理学测试。新特征的学龄前DMD男孩将被跟踪，以跟踪他们的语言和情感发展。