title: Inherited prion disease with an alanine to valine mutation at codon 117 in the prion protein gene.
abstract: A large English family with autosomal dominant segregation of presenile dementia, ataxia and other neuropsychiatric features is described. Diagnoses of demyelinating disease, Alzheimer's disease, Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker syndrome have been attributed to particular individuals at different times. An Irish family, likely to be part of the same kindred, is also described, in which diagnoses of multiple sclerosis, dementia, corticobasal degeneration and new variant CJD have been considered 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 information has been reported. Here we describe the phenotypic spectrum of inherited prion disease (PrPA117V). The diversity of phenotypic expression seen in this kindred emphasizes the logic of molecular classification of the inherited prion diseases rather than classification by specific clinicopathological syndrome. Indeed, inherited prion disease should be excluded by PRNP analysis in any individual presenting with atypical presenile dementia or neuropsychiatric features and ataxia, including suspected cases of new variant CJD.
authors.affiliation: MRC Prion Unit and Department of Neurogenetics, Imperial College School of Medicine at St Mary's, UK.
authors.forename: G R
authors.initials: GR
authors.lastname: Mallucci
authors.forename: T A
authors.initials: TA
authors.lastname: Campbell
authors.forename: A
authors.initials: A
authors.lastname: Dickinson
authors.forename: J
authors.initials: J
authors.lastname: Beck
authors.forename: M
authors.initials: M
authors.lastname: Holt
authors.forename: G
authors.initials: G
authors.lastname: Plant
authors.forename: K W
authors.initials: KW
authors.lastname: de Pauw
authors.forename: R N
authors.initials: RN
authors.lastname: Hakin
authors.forename: C E
authors.initials: CE
authors.lastname: Clarke
authors.forename: S
authors.initials: S
authors.lastname: Howell
authors.forename: G A
authors.initials: GA
authors.lastname: Davies-Jones
authors.forename: M
authors.initials: M
authors.lastname: Lawden
authors.forename: C M
authors.initials: CM
authors.lastname: Smith
authors.forename: P
authors.initials: P
authors.lastname: Ince
authors.forename: J W
authors.initials: JW
authors.lastname: Ironside
authors.forename: L R
authors.initials: LR
authors.lastname: Bridges
authors.forename: A
authors.initials: A
authors.lastname: Dean
authors.forename: I
authors.initials: I
authors.lastname: Weeks
authors.forename: J
authors.initials: J
authors.lastname: Collinge
mesh_terms: D000328:Adult; D017668:Age of Onset; D000483:Alleles; D019943:Amino Acid Substitution; D000682:Amyloid / Q000235:genetics*; D001921:Brain / Q000473:pathology; D003062:Codon / Q000235:genetics*; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D004739:England; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007494:Ireland; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009929:Organ Size; D010375:Pedigree; D010641:Phenotype; D017096:Prion Diseases / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*
chemical_list: D000682:Amyloid; D003062:Codon; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors