Trinucleotide Repeat Disorders
Part 7: Polyglutamine Diseases

Descriptions of other diseases that involve codon repeat expansions.

SCA6 (Spinocerebellar Ataxia Type 6)

SCA6 (Spinocerebellar Ataxia Type 6) is probably the simplest of all the SCAs in terms of its symptoms: People with SCA6 predominantly experience random episodes of ataxia or slowly progressing ataxia.

The Gene:

The gene involved in SCA6 lies on Chromosome 19 and is also named SCA6. Typically, in asymptomatic individuals there are between 4 and 18 copies of CAG in the SCA6 allele. In a person with the disease, however, the allele has anywhere between 21 and 33 copies. This is the smallest number of trinucleotide repeats known to cause disease. At present, not enough data exist to fully understand the effect that alleles with 19 copies of CAG will have on individuals. Individuals with 20 copies of CAG may or may not be at risk of developing SCA6. To learn more about alleles and more specifically, HD alleles, click here.

The Protein:

Instead of its own separate protein product, the SCA6 gene codes for a subunit of the calcium channels that exist in all nerve cells. This subunit, called Alpha-1A, creates a pore in the membrane of the nerve cell, allowing calcium to enter the cell and have an excitatory effect. The excited cell can then process the inputs it has received (due to calcium’s effect) and decide whether or not it should relay this information on to other nerve cells. In this way, Alpha-1A appears to play a significant role in nerve cell communication. (For more information about how nerve cells communicate, click here). In their altered form, however, Alpha-1A subunits tend to leave the membrane and aggregate in the cytoplasm inside the cell, where they clump together and do not perform their normal duties. This movement from the membrane hinders the nerve cell’s ability to receive and process messages from other nerve cells. Since communication is essential to the survival of nerve cells, the clumping of the altered Alpha-1A subunits in the cytoplasm may play a significant role in nerve cell degeneration. (See Figure F-13.)

How the Symptoms Come About:

In SCA6, the areas most affected by nerve cell damage are the cerebellum and the Purkinje cells. Given their roles in refining motions (as mentioned in the discussion of the cerebellum), one can see how damage to these areas esults in loss of coordination. Also contributing to the symptoms is degeneration of the granule cells and the nerve cells of the inferior olive. Since these structures are involved in the input of information to the cerebellum - and likewise the Purkinje cells are involved in its output - we can see that both input and output are quite important in creating smooth, precise motions. At any given time, some nerve cells may be less affected by SCA6 than others, and this may account for the random episodes of ataxia: one group of cells may be affected one day, and another group a different day. (See Figure F-14.)

Last Modified: 9-18-02

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