An Interesting SCA2 Intermediate.

Spinocerebellar ataxia 2 (SCA2) is an autosomal dominant neurodegenerative disorder characterised by ataxia, slow saccadic eye movements and opthalmoparesis. SCA2 is caused by expansion of the CAG repeat tract in exon 1 of the ataxin-2 gene (12q24). Normal alleles have between 16-30 repeats with 1-3 CAA interruptions. Pathogenic alleles have 36-52 repeats with no CAA interruptions. Intermediate alleles are extremely rare, however two SCA2 patients have been previously reported with CAA interrupted tracts of 34 repeats. Age of onset is inversely proportional to the length of the expansion. We present a patient with SCA2 symptoms and an intermediate allele. An 83 year old man was referred to us having developed cerebellar ataxia. Analysis found a CAG tract of 32 repeats at the SCA2 locus. Sequencing showed the allele to contain 2 CAA interruptions. All other SCA loci tested normal. Little is known about the pathogenicity of intermediate alleles and it is thought they may be incompletely penetrant. The presence of CAA interruptions should have no effect at the protein level as both CAA and CAG codons encode for glutamine but at the DNA level they confer stability on transmission. This intermediate allele in our elderly patient caused difficulties in counselling as it is not clear whether the intermediate allele was the cause of the patient's symptoms. We discuss some of the issues raised by the case. [ABSTRACT FROM AUTHOR]