title: Favourable mutation test outcomes for individuals at risk for Huntington disease change the perspectives of first-degree relatives.
abstract: 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 individual'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 2 (n)/(2 (n)+1) for the at-risk parent, providing that none of the offspring of this parent has been identified as a carrier. Likewise, the probability of being a non-carrier equals (2 (n+1)+1)/(2 (n+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 late-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.
authors.affiliation: Department of Medical Psychology and Psychotherapy, Netherlands Institute of Health Sciences, Erasmus MC, PO Box 1738, 3000 DR Rotterdam, The Netherlands. bonke@mpp.fgg.eur.nl
authors.forename: Benno
authors.initials: B
authors.lastname: Bonke
authors.forename: Aad
authors.initials: A
authors.lastname: Tibben
authors.forename: Dick
authors.initials: D
authors.lastname: Lindhout
authors.forename: Theo
authors.initials: T
authors.lastname: Stijnen
mesh_terms: D004252:DNA Mutational Analysis; D005260:Female; D006580:Genetic Carrier Screening; D005817:Genetic Counseling; D005838:Genotype; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis; D011336:Probability; D012306:Risk
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins