Molecular Diagnosis of Dyslexia

描述(申请人提供)：阅读障碍(RD)，也被称为阅读障碍，是影响学龄儿童的最常见的学习障碍。在美国、加拿大、欧洲和对其进行研究的国家，发病率在5%到17%之间。最突出的特征是尽管有足够的机会、指导和智力，但仍难以学习阅读。然而，研发经常得不到认可--即使是好老师--导致学习成绩不佳，在许多情况下，自尊心也很低。干预计划已被证明是有效的，但当在早期发现和治疗RD时，效果最好。最近，我们发现了一种名为DCDC2的基因，以及与RD密切相关的等位基因变异。我们开发了准确确定谁是RD等位基因携带者的方法，并可用于早期诊断。至少还有另外两个RD基因也被鉴定出来：KIAA0319和DYX1C1。这三个基因的RD等位基因在美国、加拿大和英国的RD受试者中经常存在。总体而言，遗传因素占研发的44%到75%。我们假设，在干预最有效的时候，可以通过对这三个基因的RD等位基因进行基因筛查，及早发现有RD风险的儿童；并且，准确、经济有效的基因筛查工具将有广泛的商业应用。在这个SBIR项目的第一阶段，我们建议1)组装和优化一组由DCDC2、KIAA0319和DYX1C1的RD等位基因组成的遗传标记。然后，我们将2)将标记面板应用于现有的RD DNA收集，以确定可预测RD风险的分子图谱，并在独立的现有收集中进行确认。这两个集合都来自美国国际公认的阅读中心为RD而彻底描述的主题。我们预计，这一第一阶段的应用将导致开发一种适合于人群筛查的RD分子图谱工具，从而能够进行早期诊断和有效的干预。阅读障碍(RD)，也被称为阅读障碍，是影响学龄儿童的最常见的学习障碍。在美国、加拿大、欧洲和对其进行研究的国家，发病率在5%到17%之间。然而，研发经常得不到认可，导致学校表现不佳。干预计划是有效的，但当RD在很小的时候就被认识和治疗时，效果最好。RD的大部分起源于遗传。我们建议开发一种低成本的基因筛查工具来检测RD，从而实现早期诊断和治疗，并具有广泛的商业应用。

DESCRIPTION (provided by applicant): Reading disability (RD), also known as dyslexia, is the most common learning disability affecting school children. In the US, Canada, Europe and countries where it has been studied, the incidence is between 5% and 17%. The most prominent feature is difficulty learning to read despite adequate opportunity, instruction, and intelligence. Yet frequently RD goes unrecognized - even by good teachers - leading to poor school performance and in many cases, low self-esteem. Intervention programs have been shown to work, but are most effective when RD is recognized and treated at an early age. Recently, we identified a gene, called DCDC2, and allelic variations that are strongly associated with RD. We developed methods for accurately determining who is a carrier of RD alleles and that could be used for early diagnosis. At least two other RD genes have been identified as well: KIAA0319 and DYX1C1. RD alleles from all three genes are frequently present in RD subjects in the US and Canada, and the UK. Overall, genetic factors account for 44% to 75% of RD. We hypothesize that children at risk for RD could be identified early - when intervention is most useful - by genetic screening for RD alleles from these three genes; and, that an accurate cost-effective genetic screening tool would have wide commercial applications. In Phase I of this SBIR project we propose to 1) assemble and optimize a panel of genetic markers comprised of RD alleles from DCDC2, KIAA0319, and DYX1C1. We will then 2) apply the marker panel to an extant RD DNA collection to identify molecular profiles that would be predictive of RD risk, and to confirm in an independent extant collection. Both of these collections are from subjects that have been thoroughly characterized for RD at internationally recognized reading centers in the US. We anticipate that this Phase I application will lead to the development of an RD molecular profile tool that is suitable for population screening, enabling early diagnosis and effective interventions. Reading disability (RD), also known as dyslexia, is the most common learning disability affecting school children. In the US, Canada, Europe and countries where it has been studied, the incidence is between 5% and 17%. Yet frequently RD goes unrecognized leading to poor school performance. Intervention programs work, but are most effective when RD is recognized and treated at an early age. Most of RD is genetic in origin. We propose to enable early diagnosis and treatment by developing a low-cost genetic screening tool for detecting RD with wide commercial application.