Familial Study of Severe Phonology Disorders

产品说明：（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，包括一组复杂的具有异质性潜在遗传基础的疾病。该项目的长期目标是确定与言语声音障碍有关的遗传影响，从而及早发现和治疗有风险的儿童。本研究的三个具体目标是：（1）我们将通过使用与语音产生和口头及书面语言相关的数量性状来鉴定与染色体区域连锁的同胞对亚组，以阐明基因型-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，这些亚组将完善我们的语音障碍分类系统，产生新的遗传和表型有意义的类别。(2)多代家系的收集将允许易感基因的精细定位和遗传传递模型的改进，包括对起源效应的父母的测试。(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。该项目利用了一个大的队列，充分表征核心家庭的儿童与语音障碍（N=250; DNA可用N=164个家庭），从我们以前的家庭研究。将对这些核心家系的先证者和兄弟姐妹进行纵向随访，以描述与不同染色体区域连锁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，以便建立多代系谱。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言语-声音障碍亚群将导致更准确的诊断分类，并提高我们对言语-声音障碍与阅读障碍关系的理解。治疗可以针对与不同遗传病因相关的特定认知缺陷进行调整。

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.