COGNITIVE & GENETIC ASPECTS: DUCHENNE MUSCULAR DYSTROPHY

描述（改编自申请人摘要）：本研究 建议通过测量来研究神经认知发展 诊断为杜氏症的男孩的神经心理学和遗传学特征 肌营养不良症（DMD）。 DMD提供了一个独特的机会， 基因-认知关系 DMD是一种X染色体连锁疾病， 进行性肌肉萎缩和不同程度的认知功能障碍 大约19%的DMD男孩是智力迟钝的。 目前尚不清楚是否有特定的认知特征与 但语言和即时记忆能力可能 选择性受损 据推测，智力迟钝 患有DMD的男孩可能会有突变，破坏DMD基因的大脑- 肌营养不良蛋白以及肌肉-肌营养不良蛋白的产生;并且一些 该基因的区域可能是必要的，但不是足够的，正常的， 认知发展 目前，没有研究记录 缺失位置是否与选择性认知缺陷有关 （可能反映了脑区功能受损，其中肌营养不良蛋白 是缺失的），还是一般的IQ。 彻底的神经心理学和遗传学 因此，对DMD男孩的评估可能有助于临床 对疾病的理解和对疾病的理论理解 神经认知发育 具体而言，这些研究将确定： 1)如果有的话，神经心理学特征与 和缺失位置; 2）认知概况是否反映了潜在的 假设涉及的脑功能;以及3）如果存在进行性 导致认知障碍 经验驱动，描述性 分析神经心理学特征、发育史和 100名DMD男孩及其未受影响的兄弟姐妹的缺失位置将被 在头两年完成。 更精细的打磨 神经心理学测试在下半年的赠款期间将 以初步调查结果为指导。 聚焦发展神经科学 假定基因对大脑结构和功能的作用， 将在限制性先证者和智商匹配的对照组中进行测试。 DMD男孩的纵向评估先前评估的智力 和肌肉功能将持续五年。

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.