Translational Research Advances a New Era of Prenatal Diagnosis and Newborn Screening

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Phenylketonuria, cystic fibrosis, Tay-Sachs disease, amniocentesis, chorionic villus sampling, tandem mass spectrometry

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This article provides a review of selected metabolic disorders resulting from genetic mutations and the methods used to identify them prenatally or facilitate diagnosis in the early neonatal period. Prenatal and neonatal diagnostic technologies have expanded and improved dramatically in the 21st century, as is their application in population-based screening and/or targeted assessment of at-risk couples. For instance, preimplantation genetic diagnosis has been a major advance. Emphasis herein has been placed on prototype diseases such as phenylketonuria, cystic fibrosis, and Tay-Sachs that have stimulated seminal efforts to improve medical practices in these fields. As more molecular strategies evolve, future developments in prenatal screening and diagnosis, along with newborn screening expansion, seem likely to continue rapid translation to the bedside.

Metabolic disorders resulting from genetic mutations have challenged obstetricians and pediatricians to develop diagnostic methods to identify them prenatally or in the early neonatal period [1]. The strategy of translational research has been ideal to close this gap as biotechnological advances are applied from the stage of novel laboratory developments to the practice of maternal-fetal medicine and neonatology. Although prenatal and neonatal diagnostic technologies have evolved gradually over four decades, they are expanding and changing dramatically in the 21st century, as is their application in population-based screening and/or targeted assessment of at-risk couples [1]. These changes have resulted in part from the Human Genome Project, a multicenter project supported by public and private funding geared to the sequencing of the human genome, which was completed in 2003. Clearly, the demand for prenatal genetic screening testing will continue as a result of individual and organizational advocacy efforts. In addition, advances in analytical technologies applying sophisticated cellular and molecular biology methods have increased the number and quality of tests available. Therefore, we are providing an overview with emphasis on prenatal diagnosis and suggest more comprehensive references in the bibliography [2–5]. We also recommend that the reader consult practice guidelines publications of The American College of Obstetricians and Gynecologists (ACOG) [6, 7], the American Academy of Pediatrics (AAP) [8], and the American College of Medical Genetics (ACMG) [9, 10]. For a variety of reasons, our review has focused almost exclusively on clinical care in the United States, where the variety and complexity of medical, legal, social, and ethical issues are generally greater than in other countries.

We have also taken the liberty of emphasizing certain disorders such as Tay Sachs disease and cystic fibrosis because they are prototype genetic disorders in prenatal and neonatal screening, respectively.

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Translational Science of Rare Diseases, v. 3, issue 2, p. 55-82