Inherited prion disease with an alanine to valine mutation at codon 117 inthe prion protein gene

A large English family with autosomal dominant segregation of presenile dem entia, ataxia and other neuropsychiatric features is described. Diagnoses o f demyelinating disease, Alzheimer's disease, Creutzfeldt-Jakob disease (CJ D) and Gerstmann-Straussler-Scheinker syndrome have been attributed to part icular individuals at different times. An Irish family, likely to be part o f the same kindred, is also described, in which diagnoses of multiple scler osis, dementia, corticobasal degeneration and new variant CJD have been con sidered in affected individuals. Molecular genetic studies have enabled the classification of this disease at the molecular level as one of the group of inherited prion diseases, with the substitution of valine for alanine at codon 117 of the prion protein gene (PRNP), Only three other kindreds have been described world-wide with this mutation and only limited phenotypic i nformation has been reported. Here we describe the phenotypic spectrum of i nherited prion disease (PrPA117V), The diversity of phenotypic expression s een in this kindred emphasizes the logic of molecular classification of the inherited prion diseases rather than classification by specific clinicopat hological syndrome. Indeed, inherited prion disease should be excluded by P RNP analysis in any individual presenting with atypical presenile dementia or neuropsychiatric features and ataxia, including suspected cases of new v ariant CJD,