General Characteristics

Large series of patients with various geographical origins have now been reported. Expansions of polyglutamine (polyQ) CAG coding repeats have common properties with three other neurodegenerative diseases carrying the same kind of causative mutation : Huntington's disease (HD), dentatorubro-pallidoluysian atrophy (DRPLA) and spinobulbar muscular atrophy (SBMA):21

- onset is mostly in adulthood, but some juvenile cases are observed, especially when transmitted by affected fathers;

- the disease course is progressive, unremitting and usually fatal 10-30 years after onset;

- normal and pathological alleles carry a variable number of CAG repeats, but the clinical symptoms appear above a threshold number of CAG repeats ranging from 20/21 in SCA622 to 54/55 in SCA5/MJD;23

- there is a strong negative correlation between the number of CAG repeats and the age at onset;

- the repeat sequence of the pathological alleles is unstable, except for SCA6, and its increase in size during transmission results in genetic anticipation;

Figure 1. Variation of the number of CAG repeats in spinocerebellar ataxias.3

the genes are expressed ubiquitously; and the pathological protein accumulates in neuronal inclusions in several affected but also in nonaffected tissues.

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