The Maternal and Child Health Bureau commissioned the American College of Medical Genetics to outline a process of standardization of outcomes and guidelines for state newborn screening programs and to define responsibilities for collecting and evaluating outcome data, including a recommended uniform panel of conditions to include in state newborn screening programs. The expert panel identified 29 conditions for which screening should be mandated. An additional 25 conditions were identified because they are part of the differential diagnosis of a condition in the core panel, they are clinically significant and revealed with screening technology but lack an efficacious treatment, or they represent incidental findings for which there is potential clinical significance. The process of identification is described, and recommendations are provided.

Beckwith-Wiedemann syndrome (BWS) is an autosomal dominant disorder of increased prenatal growth and predisposition to embryonal cancers such as Wilms tumor. BWS is thought to involve one or more imprinted genes, since some patients show paternal uniparental disomy, and others show balanced germ-line chromosomal rearrangements involving the maternal chromosome. We previously mapped BWS, by genetic linkage analysis, to 11p15.5, which we and others also found to contain several imprinted genes; these include the gene for insulin-like growth factor II (IGF2) and H19, which show abnormal imprint-specific expression and/or methylation in 20% of BWS patients, and p57KIP2, a cyclin-dependent kinase inhibitor, which we found showed biallelic expression in one of nine BWS patients studied. In addition, p57KIP2 was recently reported to show mutations in two of nine BWS patients. We have now analyzed the entire coding sequence and intron-exon boundaries of p57KIP2 in 40 unrelated BWS patients. Of these patients, only two (5%) showed mutations, both involving frameshifts in the second exon. In one case, the mutation was transmitted to the proband's mother, who was also affected, from the maternal grandfather, suggesting that p57KIP2 is not imprinted in at least some affected tissues at a critical stage of development and that haploinsufficiency due to mutation of either parental allele may cause at least some features of BWS. The low frequency of p57KIP2 mutations, as well as our recent discovery of disruption of the K(v)LQT1 gene in patients with chromosomal rearrangements, suggest that BWS can involve disruption of multiple independent 11p15.5 genes.

The American Recovery and Reinvestment Act has provided resources for comparative effectiveness research that will lead to evidence-based decisions about health and health care choices. Some have voiced concerns that evidence-based comparative effectiveness research principles are only relevant to "average" patients and not as much to individuals with unique combinations of genes, exposures and disease outcomes, intrinsic to genomic medicine. In this commentary, we argue that comparative effectiveness research and genomic medicine not only can and should coexist but also they will increasingly benefit from each other. The promise and success of genomic medicine will depend on rigorous comparative effectiveness research to compare outcomes for genome-based applications in practice to traditional non-genome-based approaches. In addition, the success of comparative effectiveness research will depend on developing new methods and clinical research infrastructures to integrate genome-based personalized perspectives into point of care decisions by patients and providers. There is a need to heal the apparent schism between genomic medicine and comparative effectiveness research to enhance knowledge-driven practice of medicine in the 21st century.

Abstract:The authors describe the rationale and initial development of a new collaborative initiative, the Genomic Applications in Practice and Prevention Network. The network convened by the Centers for Disease Control and Prevention and the National Institutes of Health includes multiple stakeholders from academia, government, health care, public health, industry and consumers. The premise of Genomic Applications in Practice and Prevention Network is that there is an unaddressed chasm between gene discoveries and demonstration of their clinical validity and utility. This chasm is due to the lack of readily accessible information about the utility of most genomic applications and the lack of necessary knowledge by consumers and providers to implement what is known. The mission of Genomic Applications in Practice and Prevention Network is to accelerate and streamline the effective integration of validated genomic knowledge into the practice of medicine and public health, by empowering and sponsoring research, evaluating research findings, and disseminating high quality information on candidate genomic applications in practice and prevention. Genomic Applications in Practice and Prevention Network will develop a process that links ongoing collection of information on candidate genomic applications to four crucial domains: (1) knowledge synthesis and dissemination for new and existing technologies, and the identification of knowledge gaps, (2) a robust evidence-based recommendation development process, (3) translation research to evaluate validity, utility and impact in the real world and how to disseminate and implement recommended genomic applications, and (4) programs to enhance practice, education, and surveillance. Genet Med 2009:11(7):488 -494.Key Words: decision support, genomics, information, medicine, network, public health T he ongoing success of genome wide association studies (GWAS) in uncovering genetic risk factors for many common diseases has fuelled expectations of a new era of health care based on personalized treatment, early detection, and disease prevention. 1-3 An optimal process is needed for appropriate translation of these new genomic discoveries into practice. The process should include mechanisms for developing an understanding of the relationship between these newly discovered factors and clinical outcomes (clinical validity), and the costs, benefits, and harms of genome-based technologies in real world settings (clinical utility). 4 Furthermore, the process should facilitate the development of evidence-based guidelines for the use of genomic applications 5 ; and appropriate implementation of these applications in practice, including protection of individuals and communities against discrimination based on genetic information. 6 Importantly, advances in genomics should be considered in the context of the larger forces affecting health care delivery in the United States, including escalating costs, differential access to quality health care, and a growing number of uninsured persons in ou...