ABSTRACT
In 1993, the mutation in the Holguin pedigrees was mapped to human chromosome 12 and the locus designated as Spinocerebellar Ataxia Type 2 (SCA2). S. M. Pulst et al. confirmed this location in a second pedigree of southern Italian descent and demonstrated that SCA2 showed marked anticipation of disease onset. The SCA2 gene was recently identified independently by groups using three different approaches, one of which employed positional cloning strategy. Amplification of the repeat region using flanking oligonucleotide primers showed two common alleles in normal individuals, and presence of normal allele and an allele of increased size in all SCA2 patients from three independent pedigrees. Testing of DNA samples from patients with sporadic ataxia or without obvious family history of ataxia has only rarely revealed SCA2 mutation. The identification of the SCA2 CAG repeat has now widened the scope of phenotypic analysis to smaller pedigrees and has provided an estimate of SCA2 frequency in different sets of ethnic and geographic populations.
