Clinical and molecular findings in the first identified Italian family with dentatorubral-pallidoluysian atrophy

Objectives - Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosom al dominant neurodegenerative disorder mostly observed in Japan, rarely rep orted in American and North European populations. The aim of this study is to characterize the clinical and molecular features of the first identified Italian DRPLA family. Patients and methods - We describe a 33-year-old fem ale presenting with ataxia. intellectual decline, epilepsy, and choreoathet osis with an adult age onset. Genomic DNA was isolated from peripheral bloo d lymphocytes of the patient and of her healthy family members following st andard procedures. Molecular tests were performed including genetic analysi s for SCA1, 2, and 3 (spinocerebellar ataxias), Huntington's disease (HD) a nd DRPLA, due to a possible overlapping in clinical presentation. Results - Molecular analysis revealed in our patient the presence of a pathological CAG expansion within the DRPLA gene. We have also documented the presence o f a smaller CAG expansion in her apparently healthy brother, excluding the possibility of a de novo mutation. Conclusion - We conclude that both sibli ngs may have inherited the molecular lesion from their deceased father, the mother being normal at molecular evaluation. Our kindred and a previously reported family from the island of Malta suggest that hereditary DRPLA may also be present in the Mediterranean area.