Genetic and clinical analysis of spinocerebellar ataxia type 8 repeat expansion in Italy

Background: The spinocerebellar ataxias (SCAs) are clinically heterogeneous disorders caused by triplet repeat expansions in the sequence of specific disease genes. Spinocerebellar ataxia type 8 (SCA8), originally described i n a family characterized by pure cerebellar ataxia with slow disease progre ssion, presents with expansion of combined CTA/CTG repeats. Objective: To perform SCA8 repeat expansion analysis in a heterogeneous gro up of ataxic patients, to determine the prevalence of this mutation in our patients and establish the frequency of expanded CTA/CTG repeats in a large group of control subjects. Patients: One hundred sixty-seven patients affected by sporadic, autosomal dominant and recessive hereditary ataxia were clinically examined and analy zed for SCA8 expansion. We further studied 161 control subjects and 125 pat ients with psychiatric disorders. Results: We found abnormally expanded CTA/CTG repeats in 5 ataxic patients, 3 of them characterized by pure cerebellar ataxia. One patient had vitamin E deficiency and I patient with a sporadic case was affected by gluten ata xia. No evidence of expanded alleles was found in healthy control subjects and in patients with psychiatric disorders. Conclusions: Our data support the evidence that CTG expansions may be linke d to SCA8, since the pathogenic expansions have been found only among patie nts with genetically unidentified forms of hereditary and sporadic ataxia. Patients carrying expanded alleles present peculiar phenotypic features, th us suggesting that unknown additional factors could probably predispose to the disease.