A case with a 120 base pair insertional mutation in the prion protein gene: the first case in Japan.

Familial prion diseases are associated with underlying mutations in the prion protein gene located on the short arm of human chromosome 20. The normal and wild type of the prion protein gene encodes the cellular prion protein, PrP, and it is thought that there is a post-translational modification to a disease related form, protease resistant PrP. PrP and PrP have the same amino acid sequence, but PrP is richer in b sheets. PrP is distinguished from PrP in that it is protease resistant and associated with infectivity. It is known that PrP deposition is associated with the pathological changes of spongiform degeneration, neuronal loss, and astrocytic gliosis. Underlying mutations are point mutations and octapeptide repeat (24 bp repeat) insertional mutations. In healthy people, the repeat is designated R1R2-R2-R3-R4, where only R1 is a nonapeptide and the others are octapeptides, between codon 51 and 91. Prion disease families with mutations of one, two, four, five, six, seven, eight, or nine extra octapeptide repeat insertions have been reported. We report a case with a 120 bp insertional mutation in the prion protein gene. To our knowledge, this is the first such case studied in Japan. The patient, a 45 year old woman, showed signs of dementia and cerebellar atrophy at the onset. In the next 4 years, her motor function did not become worse, though her higher brain function was deteriorating gradually. Cases with the same mutant protein have been reported in an American family, an American family of Ukrainian origin, and a German family. The clinical features of this case are very similar to those of the reported cases, but there are subtle differences in the DNA sequence of the octapeptide repeat region.