Triplet Repeats in Huntington’s Disease

This article is written by Alice Christian, Genetic Counsellor Central Regional Genetic Service’s Wellington Hospital.

 The molecular code is read in groups of three molecules called a codon. Within the HD gene there is a section where one codon (containing the molecule sequence “CAG”) is repeated many times in tandem. This is referred to as a triplet repeat. The number of triplet repeats can grow, and beyond a certain number result in some change (not yet understood) which causes HD to develop.
    The number of triplet repeats may stay the same or grow between generations. Occasionally the triplet repeat number has decreased, but this is rare. The number of triplet repeats is more likely to increase when the HD gene mutation is inherited from the father.
    In general as the number of repeats increases, the age when symptoms appear gets earlier and the symptoms progress more quickly. However, two people with the same number of repeats (even related) can be affected at very different ages, and have different progression of symptoms.

 The American College of Medical Genetics and the American Society of Human Genetics have published the following guidelines.

 There are essentially 4 categories of repeat numbers, as follows
1. Repeat numbers <26. These repeat numbers do not cause HD, nor are children at risk.
2. Repeat numbers 27-35. These repeat numbers, do not cause HD, but children may be at risk of developing HD.
3. Repeat numbers 36-39. This is associated with HD, but there may be reduced severity. Some people with these numbers may not develop HD. Children are at risk.
4. Repeat numbers > 40. HD is expected to develop within the normal life span. Children are at risk.

 These guidelines are based on current knowledge. They are subject to change as we gain more knowledge of HD.