[Genetic analysis including predictive DNA testing in a Japanese family with dentatorubral-pallidoluysian atrophy]

Dentatorubral-pallidoluysian atrophy (DRPLA) is a neurodegenerative disease showing autosomal dominant inheritance, which is associated with a specific trinucleotide repeat expansion in the DRPLA gene. We performed DNA analysis of two affected and one non-affected individuals of a Japanese family with DRPLA. The proband (case 1) developed seizures at age 17, and these gradually evolved to intractable myoclonic epilepsy. His father (case 2) had manifested gait disturbance since the age of 40, which was followed by progressive dementia. DNA analysis disclosed that these patients had an expanded CAG repeat in the DRPLA gene, which confirmed the diagnosis. The brother of case 1, who was asymptomatic, expressed a desire to undergo predictive DNA testing for DRPLA. We discussed the ethical and social issues of this predictive testing, and decided to carry out the testing after obtaining informed consent from him and his wife. The test revealed no expanded allele, thus proving that he would not develop DRPLA, and relieving him of his fears. Our results suggest that predictive testing improves the psychological well-being of non-affected individuals in DRPLA families.