In mutation testing for Huntington disease, an autosomal dominant hereditary late-onset disorder, unfavourable test outcomes in at-risk individuals provide important information about other family members at risk. On the other hand, common counselling practice considers favourable outcomes as non-informative for at-risk relatives, except for the offspring of the tested individual. We shall show, however, that favourable outcomes also change the perspectives for the tested individuals's first-degree relatives at risk. In the case of a (prospective) parent originally at 50% risk, and with n equalling the number of children or fetuses identified as non-carriers, the probability of being a non-carrier equals 2n/(2n+1) for the at-risk partent, providing that none of the offspring of this parent has been identified as a carrier. Likewise, the probability of being a non-carrier equals (2n/nn+1+2) for the (future) siblings of the tested individual. These changes in probabilities are important for individuals who are considering prenatal or presymptomatic DNA-testing for autosomal dominant hereditary lete-onset disorders, such as Huntington disease and hereditary forms of cancer (BRCA1/2, FAP, HNPCC). Consequences can be far reaching in the case of pregnancies, where the risk of miscarriage after a prenatal test is 1%-2%. Parents initially at 50% risk may consider not having a prenatal test in successive pregnancies, knowing that favourable test results in previous pregnancies have considerably reduced their personal risk.,
Human Genetics
Department of Clinical Genetics

Bonke, B, Tibben, A, Lindhout, D, & Stijnen, Th. (2002). Favourable mutation test outcomes for individuals at risk for Huntington disease change the perspectives of first-degree relatives. Human Genetics, 111(3), 297–298. doi:10.1007/s00439-002-0764-9