LINGUISTIC PHENOTYPE IN FAMILIAL DYSLEXIA

描述（改编自申请人摘要）：拟议的研究是 NIMH MERIT奖的竞争性更新，重点是语言 家族性阅读障碍的表型。 我们早期的工作已经澄清了 潜在的认知表型和遗传病因的家族性 阅读障碍 我们建议通过检查两种表型来扩展这项工作， 阅读障碍（或阅读障碍--RD）与 语音障碍（PD），表现在不同的年龄，但表现出 几个有趣的共同点 这两种疾病在病理学上是重叠的 一些对帕金森病儿童的前瞻性研究发现， RD发生率升高，在RD儿童的回顾性研究中 记录早期PD的发生率升高。 潜在的认知表型 这也是RD的特征，也就是音素意识的缺陷 在许多PD病例的随访中。 最后，有证据表明， 这两种疾病都受到遗传的影响， 共同家族的 总之，有证据表明，在三个层面上存在重叠， 分析：定义症状，潜在的认知过程和家族性 病因学 我们将测试这种重叠的五种相互竞争的解释： 它们在遗传病因学和 认知表型，但症状表现不同，这取决于 严重程度使得PD + RD是比单独RD更严重的表现; 2） 他们有一个共同的病因， PD，RD，或两者在给定的个体; 3）PD和RD具有 不同的病因，但共享一个共同的认知表型（认知 表型假说）; 4）PD和RD有不同的病因，但 PD伴随特定语言障碍发展为一种症状 RD的表型（协同作用假说）;或5）PD和RD具有不同的 病因，但由于分类（RD个体）而在后代中共同发生 更有可能与PD个体交配）。 我们将进行四个主要的测试来区分这些假设。 具体来说，我们将测试1）是否存在共同的认知表型 通过纵向研究; 2）是否存在共同的遗传 通过PD家族的连锁分析确定病因; 3）是否存在 通过检查PD和RD儿童的父母进行分类;以及4）PD，RD， PD+RD在家系中分离。

DESCRIPTION (Adapted from applicant's abstract): The proposed research is the competitive renewal of an NIMH MERIT award focused on the linguistic phenotype in familial dyslexia. Our earlier work has clarified both the underlying cognitive phenotype and the genetic etiology of familial dyslexia. We propose to extend that work by examining both the phenotypic and genotypic relation between dyslexia (or reading disability--RD) and phonological disorder (PD), which manifest at different ages but exhibit several intriguing commonalities. The two disorders overlap symptomatically in that some prospective studies of children with PD find they later have an elevated rate of RD and in that retrospective studies of children with RD document elevated rates of earlier PD. The underlying cognitive phenotype that is characteristic of RD, a deficit in phoneme awareness, is also found on follow-up in many cases of PD. Finally, there is evidence that each disorder is under genetic influence and that the two disorders are co-familial. In sum, there is evidence for overlap at three levels of analysis: defining symptoms, underlying cognitive processes, and familial etiology. We will test five competing explanations for this overlap: 1) that they are the same disorder in terms of both genetic etiology and cognitive phenotype, but that the symptom manifestations differ depending on severity such that PD + RD is a more severe manifestation than RD alone; 2) that they share a common etiology which acts pleiotropically to produce either PD, RD, or both in a given individual; 3) that PD and RD have distinct etiologies, but share a common cognitive phenotype (cognitive phenocopy hypothesis); 4) that PD and RD have distinct etiologies, but that PD accompanied by specific language impairment develops into a symptom phenocopy of RD (synergy hypothesis); or 5) that PD and RD have distinct etiologies, but co-occur in offspring because of assortment (RD individuals are more likely to mate with PD individuals). We will perform four principal tests to distinguish these hypotheses. Specifically, we will test 1) whether there is a common cognitive phenotype by means of a longitudinal study; 2) whether there is a common genetic etiology by means of a linkage analysis of PD families; 3) whether there is assortment by examining parents of PD and RD children; and 4) how PD, RD, and PD+RD segregate in families.