Sequencing analysis of the SCA6 CAG expansion excludes an influence of repeat interruptions on disease onset

Introduction

Polyglutamine (polyQ) diseases are caused by coding expanded (CAG)n repeats in the respective genes.1 Repeat instability, both germ line and somatic, is known to occur in most polyQ diseases and can influence the phenotype. Longer repeats are usually associated with earlier ages at onset (AAO) and/or more severe disease courses. Repeat instability with expansion bias can have severe clinical consequences to patients with these devastating conditions for which there are no disease-modifying treatments available. Several factors, including the size of the repeats (longer repeats are more unstable), and the presence of sequence interruptions (pure repeats are more unstable) are known to have an influence.2

Spinocerebellar ataxia type 6 (SCA6), a late-onset autosomal dominant relatively slowly progressive and pure cerebellar ataxia,3 is one of the six polyQ SCAs. SCA6 is caused by expanded (CAG)n repeats in CACNA1A. Normal alleles range from 4 to 18 CAG repeats, while...

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