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: 6802987
• 负责人: VERONICA J HINTON
• 金额: $ 38.83万
• 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 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6802987
• 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）：本研究的目的是调查诊断为杜氏肌营养不良症 (DMD) 的个体的神经心理功能，作为发育神经科学的模型。 DMD 是一种单基因疾病，会干扰肌营养不良蛋白及其亚型的表达。肌肉中缺乏抗肌营养不良蛋白的后果是众所周知的。男孩患有进行性肌肉无力，通常会在三十几岁时死亡。中枢神经系统也缺失肌营养不良蛋白同种型，但其可能产生的功能后果尚不清楚。对 DMD 的认知特征、行为属性和分子遗传学的跨学科研究将检查基因型/表型关联。该研究将建立在确定 136 名被诊断患有 DMD 的男孩的神经心理功能的基础上，该研究是在 R29 奖项任期内完成的。这些数据证实，具有平均智力的患有DMD的男孩在言语工作记忆方面存在选择性缺陷，但陈述性记忆和视觉空间技能完整，社交技能较差，语言发展里程碑延迟。从已建立的队列中选出的受试者将在重点范式中进行更彻底的检查，以使用一系列旨在检查假设的“语音循环”的测试来梳理他们的语言和短期记忆技能。此外，还将对受试者进行社会功能和意识测量的测试。还将招募新受试者以增加遗传分析的样本量。该疾病表现较轻微的受试者（患有贝克尔肌营养不良症的男孩和女性携带者）将接受神经心理学测量，以确定他们是否表现出认知表型。对 26 名男孩样本进行的纵向研究将继续进行，每隔一年进行一次神经心理学测试。新鉴定的患有 DMD 的学龄前男孩将被追踪，以追踪他们的语言和情感发展。