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.
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.
