title: Codon 200 mutation of the prion gene: genotype-phenotype correlations.
abstract: Genetic mutations as a cause of prion diseases are rare. We describe a large family with multiple affected members with the codon E200K prion mutation. To improve understanding of the genotype-phenotype correlations of prion gene mutations, clinical, genetic and neuropathological data were obtained from family members over 15 years. Six patients with the codon E200K mutation and 2 patients without the codon 200 mutation from this family were followed. The 6 patients with the codon 200 mutation had a mean age onset of 58.83 years (SD 7.2; lower 95 % CI 51.0; upper 95 % CI 66.4). The most common symptoms at onset were memory loss, walking difficulties and hallucinations. The most frequent neurological phenomena were a rapidly progressive dementia, eye movement abnormalities and ataxia. The mean duration of onset of symptoms to death was 3.9 months (SD 1.1; lower 95 % CI 2.8; upper 95 % CI 5.1). Two male patients developed neurodegenerative disorders unrelated to the prion codon 200 mutation: progressive supranuclear palsy and olivopontocerebellar degeneration. Their mean survival was 96 months (SD 33.9; p < 0.0001). Individuals from families with the prion codon 200 mutation may have a rapidly progressive dementia. Members of families with inherited prion mutations may be at risk of other neurodegenerative disorders unrelated to the prion mutation.
authors.affiliation: Neurodegenerative Disorders Research Pty Ltd, 185 York Street, Subiaco, WA 6008, Australia. research@ndr.org.au
authors.forename: Peter K
authors.initials: PK
authors.lastname: Panegyres
authors.forename: Judy G S
authors.initials: JG
authors.lastname: Goh
authors.forename: Jack
authors.initials: J
authors.lastname: Goldblatt
mesh_terms: D000368:Aged; D003062:Codon / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D017096:Prion Diseases / Q000175:diagnosis* / Q000235:genetics*; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*
chemical_list: D003062:Codon; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions