Cognitive Genetic Aspects of Duchenne Muscular Dystrophy

描述（由研究者提供）：本研究的目的是研究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是一种干扰肌营养不良蛋白及其同型异构体表达的单基因疾病。肌肉中缺乏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，通常在30岁左右死亡。在中枢神经系统中也缺失了肌营养不良蛋白同种异构体，但这可能造成的功能后果尚不清楚。认知特征、行为属性和DMD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136名诊断为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男孩在口头工作记忆、完整的陈述性记忆和视觉空间技能、糟糕的社交技能和延迟的语言发展里程碑方面存在选择性缺陷。从已建立的队列中选出的受试者将在集中的范式中进行更彻底的检查，以梳理他们的语言和短期记忆技能，使用一系列旨在检查假设的“语音循环”的测试。此外，还将测试受试者的社会功能和意识。为了增加基因分析的样本量，我们还将招募新的研究对象。症状较轻的受试者（患有贝克氏肌肉萎缩症的男孩和女性携带者）将接受神经心理学测试，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每隔一年进行一次神经心理学测试。新发现的学龄前DMD男孩将被跟踪追踪他们的语言和情感发展。

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.