Huntington disease: a detective story.

As recombinant DNA diagnoses of various inherited diseases become a standard medical procedure, the practicing physician will be required to identify families at risk and counsel them (or refer them) appropriately. In many families the risk may not be immediately obvious or a reliable risk figure may appear to be unattainable. In the case presented, the patient had an apparent 50% risk for Huntington disease and all the immediate affected relatives were deceased. This relatively common scenario would generally prevent recombinant DNA diagnostic procedures from arriving at a more accurate risk estimate. Nevertheless, by recombinant DNA analysis, a risk for Huntington disease of less than 1% was obtained. Several key aspects of genetic analysis were required including extensive family histories, identification of informative markers, ordering the markers around the disease gene and appropriate statistical analyses. These discussions illustrate the power of recombinant DNA techniques to detect genetic disorders and demonstrate why they will be of increasing importance to the practicing physician.