Familial Study of Severe Phonology Disorders

描述：（由申请人提供）：言语-声音障碍是儿童中最普遍的言语/语言障碍，包括具有异质性潜在遗传基础的复杂障碍组。该项目的长期目标是确定与言语障碍有关的遗传影响，从而及早发现和治疗处于危险中的儿童。研究将涉及三个具体目标：(1)我们将通过使用与语音产生、口语和书面语相关的数量特征来识别与染色体区域相关的兄弟姐妹亚群，以澄清基因型-表型关系，并阐明导致语音、语言和阅读障碍重叠的遗传因素。我们预计这些亚群将完善我们的语音障碍分类系统，以产生新的遗传和表型上有意义的类别。(2)收集家庭的多代谱系可以精确定位易感基因和改进遗传传递模型，包括测试原生亲本效应。(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。本项目利用了我们之前的家庭研究中大量具有良好特征的言语障碍儿童核心家庭（N=250； DNA可用N=164）。对这些核心家庭的先证和兄弟姐妹进行纵向随访，以描述语音、语言、阅读和拼写结果与不同染色体区域的连锁和表型的发育变化有关。这些家庭的大家庭成员将被邀请参加研究，以便构建多代谱系。无模型连锁和传递不平衡测试将检查染色体1、3、6、7、15、16和19的区域。识别与不同染色体区域相关的语音障碍亚群将导致更准确的诊断分类，并提高我们对语音障碍与阅读障碍之间关系的理解。治疗可以针对与不同遗传病因相关的特定认知缺陷进行量身定制。

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.