Calculating predictive values for the large repeat alleles at the SCA8 locus in patients with ataxia.

Since the original description of SCA8 in 1999, 1 several reports have been published on the occurrence of the SCA8 gene CTG repeat expansion in various populations. These studies have shown that, in addition to finding the SCA8 expansion in familial and sporadic ataxia patients, expanded alleles can also be found in non-ataxic subjects, psychiatric patients, and in patients with various other neurological diseases with a known aetiological cause. Owing to the exceptionally low penetrance of the mutation, questions have been raised about the pathogenic role of the expansion, and there exists speculation about alternative mechanisms, such as linkage disequilibrium of the CTG expansion with another as yet unidentified causal mutation. Accordingly, caution in interpreting mutation findings in clinical samples has been stressed and some investigators discourage genetic testing for SCA8 until a pathological mechanism has been established. 6