Population Screening for Hemochromatosis: The Evolving Role of Genetic Analysis

All clinicians are aware of the recent explosion of new genetic information. The number of genetic disorders with a defined molecular cause continues to increase rapidly. In turn, the successes of gene mutation analysis are reflected in the marked proliferation of genetic screening and diagnostic assays, including carrier tests. Unanticipated dividends have also resulted from gene mutation analysis. One of these is the identification of novel and unexpected mechanisms of mutation and genetic variation (for example, trinucleotide expansion and imprinting), which enhance our understanding of the intricacies of certain human genetic disorders.

The emergence of new genetic information provides unprecedented opportunities for practicing physicians to understand, diagnose, and treat genetic disorders, but much work needs to be done before medical genetic principles and genetic technology are fully integrated into clinical practice. Although a surfeit of information is available about many single gene disorders, our knowledge base is still limited in many areas of human genetics, including understanding of the pathogenesis of most genetic disorders. Moreover, few effective interventions exist for most genetic diseases.

Because genotype-phenotype correlations are still in their infancy, the prognostic value of most genetic tests is limited. The degree of penetrance of specific genotypic profiles varies widely. For example, many persons who are homozygous for a specific mutation will present with all of the cardinal clinical features of the disease in question, whereas others with the same mutations will not develop any signs or symptoms of the disorder during their lifetime. Still others will manifest mild symptoms. Although hypotheses abound to explain these phenomena, little information is available on the effect of other genes or the role of environmental factors that might help to explain these differences.