Familial Study of Severe Phonology Disorders

描述：(申请人提供)：言语-声音障碍是儿童中最常见的言语/语言障碍，包括一组复杂的障碍，具有不同的潜在遗传基础。该项目的长期目标是确定与语音障碍相关的基因影响，这将导致对处于危险中的儿童的早期识别和治疗。我们将致力于三个具体目标：(1)我们将利用与语音产生和口语和书面语相关的数量性状来鉴定与染色体区域(S)连锁的兄弟姐妹对亚群，以阐明基因-表型关系和导致语音、语言和阅读障碍重叠的遗传因素。我们预计，这些亚组将完善我们的语音-声音障碍分类系统，以产生新的遗传和表型上有意义的类别。(2)多代家系家系的收集将使易感基因(S)的精细定位和遗传传播模式的改进，包括对父母原产地效应的测试。(3)我们将测量表型的纵向变化，并确定导致这些变化的遗传因素。该项目利用了我们之前的家庭研究中的一大批特征良好的言语发音障碍儿童核心家庭(N=250；DNA可用N=164个家庭)。将对来自这些核心家庭的先证者和兄弟姐妹进行纵向跟踪，以描述与不同染色体区域的联系和表型发育变化相关的语音、语言、阅读和拼写结果。这些家庭的大家庭成员将被邀请参加这项研究，以便构建多代人的家谱。无模型连锁和传递不平衡测试将检查1、3、6、7、15、16和19号染色体的区域。识别与不同染色体区域相关的语音障碍亚组将导致更准确的诊断类别，并提高我们对语音障碍与阅读障碍之间关系的理解。治疗可以量身定做，以解决与不同遗传病因相关的特定认知缺陷。

DESCRIPTION: (provided by applicant): Speech-sound disorders are the most prevalent group of speech/language disorders in children and comprise a complex group of disorders that have a heterogeneous underlying genetic basis. The long-term goal of the project is to identify genetic influences associated with speech-sound disorders that will result in the early identification and treatment of children at risk. Three specific aims will be addressed: (1) We will identify subgroups of sibling pairs with linkage to a chromosome region(s) by employing quantitative traits associated with speech sound production and oral and written language in order to clarify genotype-phenotype relationships and elucidate genetic factors that contribute to the overlap of speech sound, language, and reading disorders. We anticipate that these subgroups will refine our classification system of speech-sound disorders to produce new genetically and phenotypically meaningful categories. (2) Collection of multigenerational pedigrees of families will allow fine mapping of the susceptibility gene(s) and refinement of genetic transmission models, including testing for parent of origin effects. (3) We will measure longitudinal changes in the phenotype and identify genetic factors contributing to these changes. This project utilizes a large cohort of well characterized nuclear families of children with speech-sound disorders (N=250; DNA available N=164 families) from our previous family study. Longitudinal follow-up of probands and siblings from these nuclear families will be conducted to describe speech-sound, language, reading, and spelling outcomes associated with linkage to various chromosome regions and developmental changes in the phenotype. Extended family members of these families will be invited to participate in the study so that multigenerational pedigrees may be constructed. Model-free linkage and transmission disequilibrium tests will examine regions of chromosome 1, 3, 6, 7, 15, 16, and 19. Identification of subgroups of speech-sound disorders associated with different chromosome regions will result in more accurate diagnostic categories and improve our understanding of the relationship of speech sound disorders to reading disorders. Therapy may be tailored to address specific cognitive deficits associated with different genetic etiologies.