PRENATAL CYTOGENETIC DIAGNOSIS BY ARRAY-BASED COPY NUMBER ANALYSES: Follow-up

描述（由申请人提供）：这是一项竞争性更新，旨在继续研究通过阵列拷贝数分析在产前诊断检测中使用分子细胞遗传学检测。我们已经完成了一个前瞻性的盲法比较拷贝数分析（aCNA）与标准的常规核型分析在4400例产前诊断试验。我们的工作表明，aCNA确定所有的病理结果所看到的核型分析，并提供了显着的增量信息，在所有患者的2%测试。这些发现使aCNA极有可能成为产前诊断的重要组成部分。然而，仍然需要重要的额外信息，以确保顺利过渡到这种新方法。 我们最初的工作已经证明了一个主要的需要，以提高我们的理解的自然历史，再进入和表达的拷贝数变异时，发现在子宫内。为了实现这一目标，我们将确定并招募超过650名母亲，她们的胎儿中有一个拷贝数变异的产前诊断。将对项目头两年招募的400多名3岁儿童进行详细的发展评估。对于与神经认知异常相关的更常见的拷贝数变异，同胞对照将进行类似的评价，以进行定量比较。来自所有参与者的数据将被纳入拷贝数变异的国家登记处，并将可用于临床和研究。将建立一个网上资源中心，提供病人支助和信息，以及补充征聘手段。 本研究还将评估拷贝数分析的咨询和教育意义，因为它被引入护理。将对患者和咨询师的经验和态度进行评估，从而制定适当的测试前和测试后指南和教育材料，并通过在线资源中心进行传播。 公共卫生相关性：分子细胞遗传学技术已被证明具有显着的优势，比传统的核型分析，并正在成为临床医学越来越重要的一部分。为了确保适当的过渡到产前诊断，我们必须有一个更好的了解自然史的小基因组不平衡时，发现在子宫内。随着越来越复杂的遗传评估被引入到患者护理中，对患者和提供者对这种转变的反应的详细研究将使我们对所需的咨询和教育要求有重要的了解。

DESCRIPTION (provided by applicant): This is a competing renewal to continue our investigations of the use of molecular cytogenetic testing by array copy number analysis in prenatal diagnostic testing. We have completed a prospective blinded comparison of copy number analysis (aCNA) with standard conventional karyotyping in 4400 unselected prenatal diagnostic tests. Our work demonstrates that aCNA identifies all pathologic findings seen by karyotyping and provides significant incremental information in 2% of all patients tested. These findings make it highly likely that aCNA will become an important part of prenatal diagnosis. However, important additional information is still required to assure a smooth transition to this new method. Our initial work has demonstrated a major need to improve our understanding of the natural history, reentrance and expressivity of copy number variants when discovered in-utero. To accomplish this, we will identify and recruit over 650 mothers with a prenatal diagnosis of a copy number variant in their fetus. Detailed developmental evaluations will be conducted at age 3 on over 400 recruited during the first two years of the project. For the more common copy number variants associated with neurocognitive abnormalities, sibling controls will undergo similar evaluations to allow quantitative comparisons. The data from all participants will be included in a national registry of copy number variants and will be available for clinical and research use. A web-based resource center will be developed providing patient support and information, as well as a supplementary means of recruitment. This study will also evaluate the counseling and educational implications of copy number analysis as it is introduced into care. Evaluation of patient and counselor experiences and attitudes will be performed leading to the development of appropriate pre and post test guidelines and educational materials that will be disseminated through an online resource center. PUBLIC HEALTH RELEVANCE: Molecular cytogenetic technologies have proven to have significant advantages over conventional karyotyping and are becoming an increasingly important part of clinical medicine. To assure appropriate transition into prenatal diagnosis we must have an improved understanding of the natural history of small genomic imbalances when discovered in-utero. Detailed study of patient and provider responses to this transition will give us an important understanding of the counseling and educational requirements needed as increasingly more sophisticated genetic evaluations are introduced into patient care.