Somatic instability of expanded CAG repeats of ATXN7 in Japanese patients with spinocerebellar ataxia type 7.

PURPOSE: Spinocerebellar ataxia type 7 (SCA7) is a disease characterized by progressive ataxia syndrome and retinal degeneration. SCA7 is caused by expansion of CAG repeats in the ataxin 7 gene. The purpose of this study was to describe the clinical and genetic features in a two-generation Japanese family with SCA7.

METHODS

The female proband underwent systemic examinations that included neurological and ophthalmic examinations and magnetic resonance imaging (MRI) scans. We interviewed her affected mother about the clinical history at the bedside. Genomic DNA was purified from peripheral blood lymphocytes. The number of CAG repeats in the proband, and her affected mother was determined by a polymerase chain reaction-based assay that used the GeneScan analysis software.

RESULTS

Neurological examinations showed limb ataxia, truncal ataxia, explosive speech, and hyperactive deep tendon reflexes. The MRI scans showed atrophy of the cerebellum and fundus of pons and tegmentum. Ophthalmologically, loss of visual acuity, macular degenerations, and central scotomas were observed in both eyes. Full-field electroretinography revealed reduced cone responses with preserved rod responses. The mother had hand-motion vision. Genetic analysis revealed that various expanded CAG repeat lengths (43-57) and the peak number of repeats (47 and 48) were the same in both patients.

CONCLUSIONS

The proband exhibited a typical phenotype of SCA7, which includes cone dystrophy and spinocerebellar ataxia. Genetic analysis demonstrated somatic instability of the CAG repeats in the blood lymphocytes and suggested that there was no genetic anticipation through the maternal transmission.