Cutaneous accumulation of abnormal polyglutamine proteins of patients with dentatorubral-pallidoluysian atrophy

Background and purpose: Dentatorubral-pallidoluysian atrophy (DRPLA) is a hereditary spinocerebellar degeneration caused by expansion of a trinucleotide CAG repeat encoding a polyglutamine tract in a disease protein atrophin-1. The clinical features include ataxia, choreoathetosis, and dementia, which result from neural degeneration caused by the mutant atrophin-1. Methods: We performed skin biopsy in two patients with DRPLA. Results: We found multiple clear cells in the epidermis, which were positive for proteins containing an expanded polyglutamine stretches. The clear cells were p63 (+), S-100 (-), and cytokeratin 20 (-), showing that they were keratinocytes. Negative or weak signals of pan-cytokeratin were consistent with the finding of decreased tonofilaments at the electron microscopic level. Conclusions: The presence of clear keratincoytes showed that the mutant proteins interfered in cellular functions not only in neural cells but also in keratinocytes. The skin is accessible by biopsy, making it important in the diagnosis. Furthermore, the polyglutamine staining in the skin may be useful for evaluation of therapeutic modalities for DRPLA and other polyglutamine diseases.