Expression profiling of peripheral blood cells in patients with different subtypes of spinocerebellar ataxias

Spinocerebellar ataxias (SCAs) are dominant, late onset hereditary disorders characterized by a progressive ataxia that is variably associated with other neurological symptoms. The clinical hallmarks result from a progressive degenerative process that mostly affects the cerebellum, brainstem and spinal cord. To date at least 25 different loci are associated with SCAs and related diseases. A large number of SCAs are caused by expanded CAG repeats within protein coding regions leading to polyglutamine tracts.

Early detection of these disorders would enable both more effective diagnosis and treatment as well as a better understanding of pathogenesis and pathophysiological processes. Therefore, we need easily accessible markers, which should i) differentiate between patients with different SCA types and ii) be detectable allready in a preclinical state of disease progression.

To achive this goal, we collected peripheral blood (PaxGene) of patients with six different SCA types as well as controls for expression profiling. Here we report the results for SCA1, 2, 3 and 6. First, we established a protocol to reduce the globin messages with magnetic beads. After hybridization of the U133 plus 2.0 Affymetrix array, expression profiles for both controls and SCA patients were analysed. Differentially expressed genes were determined that can distinguish between control samples and SCA patients as well as a set of genes which seperates SCA3 from SCA6 patients. Microarray results were validated using real-competitive RT-PCR.