The SCA12 mutation as a rare cause of spinocerebellar ataxia

Background: Spinocerebellar ataxias are a group of phenotypically and genet ically heterogeneous disorders characterized by progressive degeneration of the cerebellum. The expansion of a CAG repeat upstream of the PP2APR55 bet a gene has been recently reported as a novel cause of a dominantly inherite d ataxia (SCA12) in a kindred with limb tremor as an early feature. Objective: To explore the relative frequency of SCA12 among familial and sp oradic spinocerebellar ataxias in an ethnically diverse patient population. Methods: We used polymerase chain reaction to analyze CAG repeat size in a series of patients presenting to an ataxia clinic in California. Results: The SCA12 expansion was not detected in any of the cases investiga ted. The largest allele found had 22 repeats, a finding within the proposed nonpathogenic range. Distribution of repeat size and heterozygosity were s imilar to that described previously. Conclusions: These results, coupled with findings in other populations, ind icate that the SCA12 mutation is a rare cause of spinocerebellar degenerati on. Diagnostic testing for SCA12 should be considered in patients with cere bellum disorders and an atypical clinical phenotype, especially when tremor is initially present.