Trinucleotide Repeat Disorders
Part 6: Polyglutamine Diseases

Descriptions of other diseases that involve codon repeat expansions.

SCA3 (Spinocerebellar Ataxia Type 3 or Machado-Joseph Disease)

SCA3 (Spinocerebellar Ataxia Type 3) is also known as Machado-Joseph Disease. In addition to the loss of coordination that is common to all SCAs, the most common symptoms of SCA3 include bulging eyes, small contractions of the facial muscles, and general rigidity.

The Gene:

The gene involved in SCA3 lies on Chromosome 14 and is also named SCA3 (although the name “MJD1” is sometimes used instead). Typically, in asymptomatic individuals there are between 12 and 43 copies of CAG in the SCA3 allele. In a person with the disease, however, the allele has anywhere between 56 and 86 copies. At present, not enough data exist to fully understand the effect that alleles with between 43 and 55 copies of CAG will have on individuals.

The Protein:

The protein product of SCA3 is called ataxin-3. Although scientists do not know the exact function of the protein, they do know that it normally resides in the cytoplasm of the cell. In people who have SCA3, however, ataxin-3 is known to aggregate in the nucleus. Researchers suspect that this change of place may be key in understanding the initiation of the disease. (See Figure F-12.)

How the Symptoms Come About:

Of all the polyglutamine disorders, SCA3 is perhaps the most perplexing with regard to the relationship between the affected brain regions and the symptoms of the disease. Damage commonly occurs in the cerebellum, basal ganglia, brain stem, and spinal cord. While damage to these areas commonly affects a wide range of movements, it does not seem to explain why such things as bulging eyes and general rigidity would occur. Hopefully, more research in this area will soon uncover the mystery.

Last Modified: 9-13-02

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