Calculating risk changes after negative mutation test outcomes for autosomal dominant hereditary late-onset disorders

Abstract

We demonstrate, in a specific scenario, the effect of negative test results from relatives in families at risk for an autosomal dominant hereditary late-onset disorder. A hypothetical pedigree, of a family at risk of Huntington's disease, was used to demonstrate the consequences for the risk status of various family members in the case where relatives have been tested, and found to be mutation negative. We argue that accurate assessment of conditional probabilities in clinical genetics is important for individuals at risk for hereditary disorders with Mendelian transmission patterns; our formulae offer the opportunity - when simplifying assumptions are met - to determine the changed risk status of individuals in such cases. © 2006 Nature Publishing Group All rights reserved.