Trinucleotide Repeat Disorders
Part 1: Polyglutamine Diseases

Descriptions of other diseases that involve codon repeat expansions.

DRPLA (Dentatorubropallidoluysian Atrophy)

Like other trinucleotide repeat disorders, DRPLA (Dentatorubropallidoluysian Atrophy) affects both the mind and body. It is characterized by abrupt muscle jerking, involuntary movements, and eventual dementia. Although these symptoms are common in the men and women of all ages who have DRPLA, young people with the disease may also be affected by progressive intellectual decline.

The Gene:

The gene involved in DRPLA lies on Chromosome 12 and is also named “DRPLA”. Typically, in asymptomatic individuals there are between 6 and 35 copies of CAG in the DRPLA allele. In a person with the disease, however, the allele has anywhere between 49 and 88 copies. At present, not enough data exist to fully understand the effect that alleles with between 35 and 49 copies of CAG will have on individuals. To learn more about alleles and more specifically, HD alleles, click here.

The Protein:

The protein product of the DRPLA gene is called atrophin-1. Although scientists are not sure about its function, the leading theory is that atrophin-1 is involved in the pathway that helps insulin take effect in the body’s cells. Since insulin helps determine how cells utilize their energy, it is essential that this pathway work smoothly so that cells can function efficiently. If there is a kink in the plan, it could spell disaster for an affected nerve cell.

How the Symptoms Come About:

The nerve cells affected in DRPLA lie in many different parts of the brain. Understanding the functions of these different parts allows us to get a better understanding of why the symptoms of DRPLA are what they are: Take first the striatum and the globus pallidus. Together, these very important regions of the brain are collectively known as the basal ganglia. The basal ganglia are important because they help plan movements and thus have a large effect on motor control. Working with other parts of the brain such as the red nucleus and the dentate nucleus (which are also damaged in people with DRPLA), the basal ganglia help to regulate each and every movement we make. When neurons in this area are damaged due to DRPLA, it’s no wonder that muscle jerks and involuntary movements become common. (For a more detailed description of the basal ganglia-written in regards to Huntington’s Disease - click here). (See Figure F-1.)

The same can be said for damage to the cerebellum, which also occurs in people with DRPLA. The cerebellum is the region of the brain where learned movements are stored. When damage occurs here, movements that were once smooth and refined become more jerky and rough since they must be constantly relearned. (See Figure F-2.)

The cerebral cortex also has a large effect on movement, particularly through the parts of it called the motor cortex and somatosensory cortex. Thus, the cerebral cortex is also involved in the motor symptoms of DRPLA. However, the tasks of the cerebral cortex reach far beyond motor control. Consider the many amazing capabilities we humans have: keen senses, the ability to speak and understand language, and the fact that we can create and use such things as logic and reason. All of these characteristics stem from functions of the cerebral cortex. Thus, when damage occurs to specific parts of the cerebral cortex, the tasks that these parts work to accomplish may become less refined. This loss of refinement may explain why people with DRPLA experience dementia when the nerve cells in the cerebral cortex are damaged. It may also partly explain the general intellectual decline in juvenile cases of DRPLA. (See Figure F-3).

Last Modified: 9-18-02

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