Juvenile HD
Part 2

The symptoms and characteristics of juvenile Huntington’s disease.

What causes the large CAG repeat numbers seen in juvenile HD cases?

Children with juvenile HD usually have a larger number of CAG repeats in a particular segment of the Huntington gene than do individuals with adult-onset HD. In many cases, these children also have many more CAG repeats compared to the parents from whom they inherited the HD allele. The exact cause of repeat expansion is still unclear. At one point, it was thought that the DNA from the unaffected parent might somehow contribute to the development of juvenile HD. A non-HD allele from the unaffected parent could potentially “aggravate” the Huntington gene and somehow cause the large increase in repeat numbers characteristic of juvenile HD. Given that juvenile HD is so rare, if there existed an allele that aggravated the disease, it would necessarily be rare as well. A case study in the 1960’s showed a man with adult-onset HD who had affected children with two different women. In order for this to occur, both of the mothers must have had the rare “aggravating allele,” a highly improbable occurrence. This finding made it seem unlikely that DNA from the unaffected parent was contributing to the expanded repeats.

Alternately, it is possible that repeat expansion is caused by DNA copying inaccuracies during cell division. Each time a cell divides, its DNA must be copied, or replicated, so that the new cell has a duplicate copy of the original DNA. (For more information on DNA, click here.) Along with this process comes the possibility that a mistake is made somewhere during the copying procedure. Such "mistakes" are very common during DNA replication. One such mistake might cause the number of codon repeats to increase. Since the formation of sperm involves millions of cell divisions more than the formation of eggs, the number of opportunities for triplet expansion during DNA replication is much larger in males than in females. Hence, it is possible that adult males are more likely to pass alleles with expanded repeat numbers to their children. We will call this the “paternal triplet expansion hypothesis.” This hypothesis could explain why in most cases (about 70-90% of them), individuals with juvenile HD have inherited the HD allele from their fathers rather than their mothers.

Last Modified: 6-9-04

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