Hereditary hemochromatosis: Gene discovery and its implications for population-based screening

Wylie Burke, Elizabeth Thomson, Muin J. Khoury, Sharon M. McDonnell, Nancy Press, Paul C. Adams, James C. Barton, Ernest Beutler, Gary Brittenham, Allen Buchanan, Ellen Wright Clayton, Mary E. Cogswell, Eric M. Meslin, Arno G. Motulsky, Lawrie W. Powell, Elliott Sigal, Benjamin S. Wilfond, Francis S. Collins

    Research output: Contribution to journalReview article

    257 Scopus citations

    Abstract

    Objective. - To evaluate the role of genetic testing in screening for hereditary hemochromatosis to help guide clinicians, policymakers, and researchers. Participants. - An expert panel was convened on March 3, 1997, by the Centers for Disease Control and Prevention (CDC) and the National Human Genome Research Institute (NHGRI), with expertise in epidemiology, genetics, hepatology, iron overload disorders, molecular biology, public health, and the ethical, legal, and social implications surrounding the discovery and use of genetic information. Evidence. - The group reviewed evidence regarding the clinical presentation, natural history, and genetics of hemochromatosis, including current data on the candidate gene for hemochromatosis (HFE) and on the ethical and health policy implications of genetic testing for this disorder. Consensus Process. - Consensus was achieved by group discussion confirmed by a voice vote. A draft of the consensus statement was prepared by a writing committee and subsequently reviewed and revised by all members of the expert group over a 1-year period. Conclusions. - Genetic testing is not recommended at this time in population- based screening for hereditary hemochromatosis, due to uncertainties about prevalence and penetrance of HFE mutations and the optimal care of asymptomatic people carrying HFE mutations. In addition, use of a genetic screening test raises concerns regarding possible stigmatization and discrimination. Tests for HFE mutations may play a role in confirming the diagnosis of hereditary hemochromatosis in persons with elevated serum iron measures, but even this use is limited by uncertainty about genotype- phenotype correlations. To address these questions, the expert group accorded high priority to population-based research to define the prevalence of HFE mutations, age and sex-related penetrance of different HFE genotypes, interactions between HFE genotypes and environmental modifiers, and psychosocial outcomes of genetic screening for hemochromatosis.

    Original languageEnglish (US)
    Pages (from-to)172-178
    Number of pages7
    JournalJournal of the American Medical Association
    Volume280
    Issue number2
    DOIs
    StatePublished - Jul 8 1998

    ASJC Scopus subject areas

    • Medicine(all)

    Fingerprint Dive into the research topics of 'Hereditary hemochromatosis: Gene discovery and its implications for population-based screening'. Together they form a unique fingerprint.

  • Cite this

    Burke, W., Thomson, E., Khoury, M. J., McDonnell, S. M., Press, N., Adams, P. C., Barton, J. C., Beutler, E., Brittenham, G., Buchanan, A., Clayton, E. W., Cogswell, M. E., Meslin, E. M., Motulsky, A. G., Powell, L. W., Sigal, E., Wilfond, B. S., & Collins, F. S. (1998). Hereditary hemochromatosis: Gene discovery and its implications for population-based screening. Journal of the American Medical Association, 280(2), 172-178. https://doi.org/10.1001/jama.280.2.172