How Is Predictive Testing Done?

The following example illustrates how predictive testing may be done in a family. Mary has requested predictive testing. Her father, John, has Huntington disease. A sample of her father’s DNA is analyzed and it is determined that he has 15 repeats on one chromosome and 45 repeats on the other. The fact that he has a gene with 45 repeats supports the clinical diagnosis of HD. Her mother does not have HD, and each of her chromosomes contain 10 repeats.

Mary’s DNA can then be assessed. If she has received 10 repeats and 45 repeats, the 10 must have come from her mother and the 45 repeats must have been inherited from her father. This indicates that she has also inherited the disease-causing version of the HD gene. If, on the other hand, she has inherited 10 repeats and 15 repeats, she received the gene containing the 15 repeats from her father. This version of the gene will not cause HD. Predictive testing is most informative and accurate when blood from an affected family member is available. However, Mary could still have been tested if blood from either parent was unavailable, and her DNA analysed to see if the number of repeats falls into the normal range.

Predictive testing provides virtually a 100% certain answer as to whether Mary has or has not inherited the gene causing HD. It does not, however, say anything about her current health with respect to Huntington disease.

Predictive testing may not be possible in a small number of families. This may occur if the clinical diagnosis in the family is HD, but none of the affected individuals in the family demonstrates the increased number of repeats found in the HD gene. This is most likely because the family has been misdiagnosed with HD but could also be because there is another change in the gene causing HD that we do not yet know how to detect. It is also possible that the individual at risk may have repeats which fall into the intermediate range. In this case, clearer results may be possible after the laboratory has had the opportunity to do some further testing or to obtain more blood samples from additional family members.