The phenotypic expression of different mutations in transmissible human spongiform encephalopathy.
Clinical, pathological, and experimental transmission characteristics are reviewed for each of the known mutations in the amyloid precursor gene (PRNP) associated with familial spongiform encephalopathies. All mutation groups show an earlier age at onset and longer duration of illness than sporadic disease, and more or less distinctive patterns of illness can be recognized for each mutation, although much variability may occur even among affected members of the same family. Experimental transmission of disease has been accomplished for most of the mutations, with shortened incubation periods in the inoculated animals that parallel the earlier age at onset of human illness in these cases, implying a shortened pre-clinical phase of disease rather than an earlier 'infecting event'. Mutations thus not only predispose to spongiform encephalopathy, but also accelerate its pathogenetic tempo and influence its phenotypic expression.
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Laboratory of CNS Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
D000682:Amyloid / Q000235:genetics; D003062:Codon / Q000235:genetics; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics; D005260:Female; D016098:Gerstmann-Straussler-Scheinker Disease / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D017096:Prion Diseases / Q000235:genetics* / Q000635:transmission
D000682:Amyloid; D003062:Codon