EXPANDED CAG REPEATS IN SWEDISH SPINOCEREBELLAR ATAXIA TYPE-7 (SCA7) PATIENTS - EFFECT OF CAG REPEAT LENGTH ON THE CLINICAL MANIFESTATION

Spinocerebellar ataxia 7 (SCA7) is a neurodegenerative disorder charac terized by degeneration of the cerebellum, brainstem and retina. The g ene responsible for SCA7, located on chromosome 3p, recently was clone d and shown to contain a CAG repeat in the coding region of the gene, that is expanded in SCA7 patients of French origin, We examined the SC A7 repeat region in four Swedish SCA7 families as well as in 57 health y controls, All Swedish SCA7 patients exhibited expanded CAG repeats w ith a strong negative correlation between repeat size and age of onset , The repeat length in SCA7 patients ranged from 40 to >200 repeats, T he largest expansion was observed in a juvenile case with an age of on set of 3 months, and represents the longest polyglutamine stretch ever reported, In patients with 59 repeats or more, visual impairment was the most common initial symptom observed, while ataxia predominates in patients with <59 repeats. Two of the Swedish SCA7 families analysed in this study were shown to be related genealogically, The other two S CA7 families could not be traced back to a common ancestor, All four f amilies shared the same allele on the disease chromosome at a locus cl osely linked to SCA7, suggesting the possibility of a founder effect i n the Swedish population.