A new PRNP mutation (G131V) associated with Gerstmann-Sträussler-Scheinker disease.
BACKGROUND
Gerstmann-Sträussler-Scheinker disease is a rare form of prion disease.


OBJECTIVE
To determine the prion mutation in a 51-year-old man without a family history of neurologic disease who died from Gerstmann-Sträussler-Scheinker disease.


METHODS
The patient was a 51-year-old man who died after a 9-year illness characterized by dementia and eventually ataxia. Neuropathologic studies were performed, the results of which revealed abundant prion protein-immunopositive amyloid plaques in the cerebellum without spongiform degeneration.


RESULTS
Genetic analysis of the prion protein gene showed a novel mutation at codon 131 that caused a valine-for-glycine substitution (G131V) and homozygosity at codon 129 (129M). Proteinase K-resistant prion protein was detected by Western blot analysis.


CONCLUSIONS
This is the first mutation described in the short, antiparallel beta-sheet domain of the prion protein. This report highlights the importance of genetic analysis of patients with atypical dementia even in the absence of a family history.
Panegyres
P K
PK
Department of Neuropathology, Royal Perth Hospital, Wellington Street, Perth, Western Australia 6000. peter.panegyres@rph.health.wa.gov.au
Toufexis
K
K
Kakulas
B A
BA
Cernevakova
L
L
Brown
P
P
Ghetti
B
B
Piccardo
P
P
Dlouhy
S R
SR
D001483:Base Sequence; D001921:Brain / Q000473:pathology* / Q000502:physiology; D016098:Gerstmann-Straussler-Scheinker Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011328:Prions / Q000032:analysis / Q000235:genetics*
D011328:Prions