Trinucleotide Repeat Disorders
Part 5: Polyglutamine Diseases

Descriptions of other diseases that involve codon repeat expansions.

SCA2 (Spinocerebellar Ataxia Type 2)

SCA2 (Spinocerebellar Ataxia Type 2) is characterized by a general slowing of some of the body’s normal processes. In addition to the loss of coordination that is common to all SCAs, people with SCA2 often develop slow or nonexistent reflexes and tend to shift the focus of their eyes from one point to another in a very deliberate manner. Partial paralysis of the eyes has even been described in some cases.

The Gene:

The gene involved in SCA2 lies on Chromosome 12 and is also named SCA2. Typically, in asymptomatic individuals there are between 14 and 31 copies of CAG in the SCA2 allele. In a person with the disease, however, the allele has anywhere between 36 and 64 copies. Individuals with between 31 and 36 copies of CAG may or may not develop the symptoms of the disease (individual results vary).

The Protein:

The protein product of SCA2 is called ataxin-2. So far, although the exact function of this protein is unknown, scientists believe that it may be involved in aiding protein-protein interaction within the cell. This would make it something of a “mediator” of communications within the cell. If this theory is correct, then when the protein is in its altered form in people with SCA2, it cannot do the same mediation that the normal form does. This loss of normal function means that essential protein-protein interactions cannot be as efficient as they were with the normal ataxin-2 involved. The end result is that the health of the cell is compromised. (See Figure F-9.)

How the Symptoms Come About:

The mechanism for the loss of coordination experienced in SCA2, due primarily to damage to the cerebellum, is more-or-less the same as the mechanism described for SCA1. (Read more about the cerebellum by clicking here.) The symptoms involving the eyes, however, result from SCA2’s effect on a different part of the brain. This region is called the midbrain. The primary function of the midbrain is to control the movement of the eyes. When neurons in this area are damaged, the eye’s movements become slower than normal and even partial eye paralysis can occur. Both of these phenomena are symptoms of SCA2. (See Figure F-10.)

The effect of SCA2 on the reflexes is explained by the damage it inflicts on the granule cells. A granule cell is a specific type of nerve cell that forwards a great deal of information on to the cerebellum. Much of this information involves the positions and movements of the limbs, as well as what parts of the skin are being stimulated at any given time. In terms of reflexes, all of this information is very important. As an example, suppose that someone is burned by a hot plate: The person must know not only what body part this sensation is coming from, but also where this part is located in space and what direction to move it in order to stop the pain. If this information is slow in getting to the brain, it can delay the reflex that is needed to deal with the pain. This slower flow of information occurs when the granule cells are damaged, causing people with SCA2 to develop slower reflexes. (See Figure F-11.)

Last Modified: 9-18-02

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