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，以继续我们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的研究。我们已经完成了一项前瞻性盲法比较拷贝数分析（aCNA）与标准常规核型在4400未选择产前诊断测试。我们的研究表明，aCNA可以识别所有通过核型分析发现的病理结果，并在2%的测试患者中提供显著的增量信息。这些发现使得aCNA极有可能成为产前诊断的重要组成部分。然而，为了确保顺利过渡到这种新方法，还需要重要的附加信息。我们的初步工作表明，主要需要提高我们对子宫内发现的拷贝数变异的自然历史、再进入和表达性的理解。为了实现这一目标，我们将确定并招募超过650名产前诊断胎儿拷贝数变异的母亲。在项目头两年招募的400多名儿童将在3岁时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，兄弟姐妹对照将进行类似的评估，以便进行定量比较。所有参与者的数据将被纳入国家拷贝数变异登记处，并可用于临床和研究。将开发一个基于网络的资源中心，为患者提供支持和信息，以及补充招聘手段。本研究也将评估在照护中引入拷贝数分析的咨询和教育意义。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后指南和教育材料，这些材料将通过在线资源中心传播。

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.