Genetics of Autism and other Communication Disorders

描述(申请人提供)：本研究项目的目标是 迅速推进目前关于自闭症的遗传学研究。我建议 现有的遗传(即基因组筛选)研究结果较少 由于自闭症谱系患者之间的异质性，所以是决定性的 精神错乱。即使根据严格和一致的标准进行诊断 (例如，自闭症诊断量表)，自闭症患者的症状特征 差异很大，表明病因学上的可变性。因此，我建议确定 确认一种可能的自闭症亚型，我称之为“发育型” 发育性语言障碍(DVD)是一种运动语言 编程混乱导致难以协调和排序 产生和组合语音(音素)所必需的口腔运动 组成音节、单词、短语和句子。我假设有一个相当大的 少数患有自闭症的轻度或不会说话的人的特点是 发育性语言障碍。对我的假设的支持来自于行为， 遗传学和神经解剖学证据。在正在进行的研究中(在合作中 与Hill Goldsmith)我正在通过以下方式识别和验证自闭症的DVD亚型 对大都市地区所有自闭症儿童(18岁以下)进行筛查； 识别也以DVD为特征的该组成员； 选择不以DVD和A为特征的自闭症对照组 典型的发展对照组；收集广泛的行为，医学， 和这些群体中所有儿童的发展史；获得 神经解剖学(结构磁共振)数据；以及收集和存储DNA。目标是 本研究会的研究培训之一是构建DVD的索引 以前使用过的诊断仪器的亚型 进行基因组筛查(例如，ADI和A-DOS)，并将这些指数应用于 识别自闭症DVD候选基因区域的现有屏幕数据 子类型。

DESCRIPTION (provided by applicant): The goal of this research project is to advance rapidly the current genetic research on autism. I suggest that the existing results of genetic (i.e., genome screen) studies have been less definitive because of the heterogeneity among persons with autistic spectrum disorders. Even when diagnosed according to strict and consistent criteria (e.g., the Autism Diagnostic Inventory), symptom profiles of persons with autism vary greatly, suggesting variability in etiology. Thus, I propose to identify and validate a putative subtype of autism, which I refer to as "developmental verbal dyspraxia." Developmental verbal dyspraxia (DVD) is a motor-speech programming disorder resulting in difficulty coordinating and sequencing the oral-motor movements necessary to produce and combine speech sounds (phonemes) to form syllables, words, phrases, and sentences. I hypothesize that a sizable minority of minimally or nonverbal persons with autism are characterized by developmental verbal dyspraxia. Support for my hypothesis comes from behavioral, genetic, and neuroanatomical evidence. In ongoing research (in collaboration with Hill Goldsmith) I am identifying and validating a DVD subtype of autism by screening all children with autism (under age 18) in a metropolitan area; identifying the members of this group who are also characterized by DVD; selecting an autism control group of children not characterized by DVD and a typically developing control group; collecting extensive behavioral, medical, and developmental histories of all children in these groups; obtaining neuroanatomical (structural MRI) data; and collecting and storing DNA. The goal of the research training for this fellowship is to construct indices of the DVD subtype from the diagnostic instruments that have been used in the previously conducted genome screens (e.g., the ADI and A-DOS) and apply those indices to the existing screen data to identify candidate gene regions for the autism-DVD subtype.