Molecular Diagnosis of Dyslexia

描述（由申请人提供）：阅读障碍（RD），也称为阅读障碍，是影响学童的最常见学习障碍。在美国，加拿大，欧洲和已进行研究的国家，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，RD往往得不到承认-即使是优秀的教师-导致学校成绩不佳，在许多情况下，自尊心低下。干预计划已被证明是有效的，但最有效的是在早期发现和治疗RD。最近，我们发现了一个基因，称为DCDC 2，和等位基因变异，与RD密切相关。我们开发了准确确定谁是RD等位基因携带者的方法，可用于早期诊断。至少有两个其他的RD基因也已被确定：KIAA 0319和DYX 1C 1。来自所有三种基因的RD等位基因经常存在于美国、加拿大和英国的RD受试者中。总体而言，遗传因素占RD的44%至75%。我们假设，儿童在风险RD可以早期确定-干预是最有用的-通过遗传筛查RD等位基因从这三个基因，准确的成本效益的遗传筛查工具将有广泛的商业应用。在SBIR项目的第一阶段，我们建议1）组装和优化一组由来自DCDC 2、KIAA 0319和DYX 1C 1的RD等位基因组成的遗传标记。然后，我们将2）将标记物组应用于现存RD DNA集合，以鉴定可预测RD风险的分子谱，并在独立的现存集合中进行确认。这两个集合都来自已在美国国际公认的阅读中心进行了全面RD表征的受试者。我们预计，这一I期申请将导致研发分子谱工具的开发，该工具适用于人群筛查，从而实现早期诊断和有效干预。阅读障碍（RD），也被称为诵读困难，是影响学童最常见的学习障碍。在美国，加拿大，欧洲和已进行研究的国家，发病率在5%至17%之间。然而，RD往往得不到承认，导致学校表现不佳。干预计划是有效的，但最有效的是在早期发现和治疗RD。大多数RD是遗传性的。我们建议通过开发一种低成本的基因筛查工具来检测RD，以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.