Trinucleotide Repeat Disorders
Part 4: Polyglutamine Diseases

Descriptions of other diseases that involve codon repeat expansions.

SCA1 (Spinocerebellar Ataxia Type 1)

SCA1 (Spinocerebellar Ataxia Type 1) is one of many closely related disorders collectively known as spinocerebellar ataxias (SCAs). Like all of the SCAs, SCA1 is characterized by atrophy of the cerebellum, a phenomenon that plays a role in the major symptoms of the disorder like loss of coordination and difficulty in articulating speech. Another common symptom of the disorder is decreased sensation in the limbs.

The Gene:

The gene involved in SCA1 lies on Chromosome 6 and is also called SCA1. Typically, in asymptomatic individuals there are between 6 and 44 copies of CAG in the SCA1 allele. In alleles with more than 20 copies (but still less than 44), the codon CAT interrupts the string of CAGs 1-4 times in a way that adds stability to the CAG chain. In a person with the disease, however, these stabilizing CATs are not present and the allele has anywhere between 39 and 81 copies of CAG. Thus, especially in the 39-44 CAG repeat range (where one may or may not be at risk for the disease), the CATs are very important—their existence can make the difference between having the illness and not.

The Protein:

The protein product of the SCA1 gene is called ataxin-1. Many studies of ataxin-1 have led scientists to believe that its major function may be to facilitate the maneuvering of nerve cell connections to allow learning. However, it is important to note that the symptoms of SCA1 are not directly caused by the loss of normal ataxin-1 function. Instead, it is believed that the cause of disease lies in the interaction between ataxin-1 and another protein called LANP. Scientists believe that LANP has a major effect on cell communication, which is needed for the survival of a nerve cell. When the ataxin-1 is altered, its interaction with LANP is also altered. The ataxin-1 is said to “sequester” the LANP and thus interfere with its normal activity. After a time, the sequestering of LANP appears to cause degeneration of the nerve cell.

How the Symptoms Come About:

To best explain how the symptoms of SCA1 come about, it is helpful to have an understanding of the cerebellum. (For more on the cerebellum, click here.)

Add to the equation a loss of pyramidal nerve cells (cells of a different pathway that are also involved in performing highly-skilled motions) and one can see why SCA1 can have such a large effect on one’s ability to perform movements.

The decreased sensation in the limbs of people with SCA1 is known as peripheral neuropathy. This condition comes about when the nerve cells that pass information from the limbs to the spinal cord (and on up to the brain) are damaged. Since they cannot do their jobs to maximum effectiveness, some of the sensory information is lost and this results in the decreased sensation.

Last Modified: 9-13-02

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