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

描述(由申请人提供)：这是一个竞争性的更新，以继续我们对通过阵列拷贝数分析在产前诊断测试中使用分子细胞遗传学测试的研究。在4400例非选择性产前诊断试验中，我们完成了拷贝数分析(ACNA)与标准常规核型的前瞻性盲法比较。我们的工作表明，ACNA确定了所有核型所见的病理结果，并在所有测试的2%的患者中提供了显著的增量信息。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，仍然需要重要的补充信息来确保向这一新方法的平稳过渡。我们的初步工作表明，当在子宫内发现拷贝数变体时，我们需要提高对自然历史、重入和表达能力的理解。为了做到这一点，我们将识别并招募650多名产前诊断出胎儿中存在拷贝数变异的母亲。将在3岁时对项目头两年招募的400多名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，兄弟姐妹对照将接受类似的评估，以进行定量比较。来自所有参与者的数据将被纳入国家拷贝数变异登记，并将用于临床和研究。将开发一个基于网络的资源中心，提供患者支持和信息，以及一种补充的招聘手段。这项研究还将评估拷贝数分析在引入CARE时的咨询和教育意义。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和测试后指南和教育材料，并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.