These insights may help to understand pathogenesis and tissue specificity in SCA2 and other polyQ ataxias like SCA1, where inositol regulation of calcium flux and RORalpha play a role.
Seven patients from four (14%) families were positive for an expansion in SCA1 and 26 patients from 16 (57%) families were positive for an expansion in SCA2.
The SCA2 mutation accounts for 8.6% of ADCA type I families referred to us, intermediate between SCA1(1.7%) and SCA3/MJD (24%) of the ADCA type I families in our collection.
The recent demonstration that spinocerebellar ataxia type 2 (SCA2) is caused by a CAG repeat expansion within the ataxin-2 gene has allowed us to determine the frequency of SCA2 compared with SCA1, SCA3/Machado-Joseph disease (MJD), and dentatorubropallidoluysian atrophy (DRPLA) in patients with sporadic and inherited ataxia.
We describe the results of genotypic analysis for the SCA2 repeat in individuals with ADSCA who were previously found negative for CAG repeat expansions in the SCA1, SCA3, or SCA6 genes.
The SCA2 phenotype differed from those of SCA1 and SCA3 with higher frequencies of slowed ocular movements, postural and action tremor, myoclonus, and hyporeflexia.
Autosomal dominant cerebellar ataxia type I. Clinical and molecular study in 36 Italian families including a comparison between SCA1 and SCA2 phenotypes.
It is possible that trinucleotide repeat expansions will underlie other hereditary neuromuscular disorders, for example spinocerebellar ataxia type 2 (mapped to 12q and with similar symptoms to SCA1 including anticipation) is a prime candidate (30).
Investigation of linkage to the interval containing SCA2 for seven French ADCA families, previously excluded from linkage to SCA1, provides preliminary data suggesting the existence of a third ADCA locus (SCA3).