COGNITIVE & GENETIC ASPECTS: DUCHENNE MUSCULAR DYSTROPHY

描述(改编自申请人的摘要)：这项研究 建议通过测量来研究神经认知发展 诊断为杜兴综合征的男童的神经心理和遗传学特征 肌营养不良(DMD)。DMD提供了一个独特的机会来检查 基因-认知关系。DMD是一种X连锁疾病，它会导致 进行性肌萎缩和不同程度的认知功能 智力障碍；大约19%的患有DMD的男孩是智力低下的。 目前尚不清楚特定的认知特征是否与 但语言和即刻记忆能力可能会 选择性受损。据推测，智障人士 患有DMD的男孩可能有突变，扰乱了DMD基因的大脑- 肌营养不良蛋白和肌肉肌营养不良蛋白的产生； 对于正常来说，基因的区域可能是必要的，但不是充分的。 认知发展。目前，还没有研究记录 缺失位置是否与选择性认知缺陷有关 (可能反映了dystrophin所在区域的脑功能受损 失踪)，或一般智商。彻底的神经心理学和遗传学 因此，对DMD男孩的评估可以在临床上做出贡献 对无序的认识和对精神错乱的理论认识 神经认知发展。具体地说，研究将确定： 1)神经心理特征之间存在什么关系(如果存在 和删除位置；2)认知特征是否反映潜在的 被认为与脑功能有关；3)如果有进行性脑功能障碍 导致认知障碍的过程。经验驱动、描述性的 神经心理学特征、发展史及相关因素分析 在100名DMD男孩及其未受影响的兄弟姐妹中的缺失位置将是 在头两年内完成。更精致的磨练 资助期后半段的神经心理测试将 以最初的调查结果为指导。聚焦发展神经科学 假设基因作用于大脑结构，从而影响大脑功能， 将在受限制的先证者和智商匹配的对照组中进行测试。 DMD男童智力状况的纵向评估 肌肉功能将持续到五年。

DESCRIPTION (Adapted from the Applicant's Abstract): This study proposes to investigate neurocognitive development by measuring neuropsychological and genetic profiles of boys diagnosed with Duchenne muscular dystrophy (DMD). DMD provides a unique opportunity to examine gene-cognition relationships. DMD is an X-linked disorder that causes progressive muscular atrophy and varying degrees of cognitive impairment; about 19 percent of boys with DMD are mentally retarded. It remains unclear whether a specific cognitive profile is associated with the disorder, but verbal and immediate memory skills may be selectively impaired. It has been hypothesized that mentally retarded boys with DMD may have mutations that disrupt the DMD gene's brain- dystrophin as well as muscle-dystrophin production; and that some regions of the gene may be necessary, but not sufficient, for normal cognitive development. At present, there are no studies documenting whether deletion positions are related to selective cognitive deficits (perhaps reflecting impaired function of brain areas where dystrophin is missing), or to general IQ. A thorough neuropsychological and genetic evaluation of DMD boys could therefore contribute both to clinical understanding of the disorder and to theoretical understanding of neurocognitive development. Specifically, the studies will determine: 1) what, if any, relationship exists between neuropsychological profile and deletion position; 2) whether cognitive profiles reflect underlying brain function presumed to be involved; and 3) if there is a progressive course to the cognitive impairment. Empirically driven, descriptive analyses of neuropsychological profile, developmental history and deletion position in 100 DMD boys and their unaffected siblings will be completed during the first two years. More finely honed neuropsychological testing in the second half of the grant period will be guided by initial findings. Focused developmental neuroscience hypotheses of presumed gene role on brain structure, and hence function, will be tested in restricted proband and IQ-matched comparison groups. Longitudinal assessment of DMD boys previously assessed on intellectual and muscle function will be continued through the five years.