Molecular Diagnosis of Dyslexia

描述（由申请人提供）：阅读障碍（RD），也被称为阅读障碍，是影响学龄儿童最常见的学习障碍。在美国、加拿大、欧洲和研究过该病的国家，发病率在5%至17%之间。最突出的特点是，尽管有足够的机会、指导和智力，学习阅读还是很困难。然而，学习障碍常常得不到认可——即使是优秀的教师——从而导致学习成绩不佳，在许多情况下还导致自尊心低下。干预方案已被证明是有效的，但当RD在早期被识别和治疗时是最有效的。最近，我们发现了一种名为DCDC2的基因和与RD强烈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。至少另外两个RD基因也已被确定：KIAA0319和DYX1C1。来自这三种基因的RD等位基因经常出现在美国、加拿大和英国的RD受试者中。总的来说，遗传因素占RD的44%至75%。我们假设，有RD风险的儿童可以通过对这三个基因的RD等位基因进行遗传筛查，在干预最有用的时候及早发现；而且，一种精确的、经济有效的基因筛选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)组装和优化由来自DCDC2、KIAA0319和DYX1C1的RD等位基因组成的遗传标记面板。然后，我们将2)将标记面板应用于现存的RD DNA收集，以确定可预测RD风险的分子谱，并在独立的现存收集中进行确认。这两本书的主题都是在美国国际公认的阅读中心进行过深入研究的。我们预计，这一I期应用将导致RD分子谱工具的发展，该工具适用于人群筛查，实现早期诊断和有效干预。阅读障碍（RD），也被称为阅读障碍，是影响学龄儿童最常见的学习障碍。在美国、加拿大、欧洲和研究过该病的国家，发病率在5%至17%之间。然而，RD经常被忽视，导致学校表现不佳。干预计划是有效的，但当RD在早期被识别和治疗时是最有效的。大多数RD是遗传的。我们建议通过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.