title: Prion mutation D178N with highly variable disease onset and phenotype.
abstract: Hereditary prion disease is a fatal genetic disorder of autosomal dominant inheritance. Recent phenotype-genotype correlation studies revealed a considerable clinical and pathological overlap for patients with the D178N mutation, suggesting a continuous spectrum between fatal familial insomnia and Creutzfeldt-Jakob Disease phenotype. This report adds further evidence to this thesis from a large German prion pedigree with D178N mutation in the PRNP-gene. This pedigree shows an extensive variability in (1) age of disease onset, ranging from 19 to 72 years and including an asymptomatic 73-year-old gene carrier and (2) disease phenotype, including a Gerstmann-Straussler-Scheinker phenotype. These findings have substantial importance for genetic counselling of persons at risk.
authors.affiliation: Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Synofzik
authors.forename: P
authors.initials: P
authors.lastname: Bauer
authors.forename: L
authors.initials: L
authors.lastname: Schöls
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D002869:Chromosome Aberrations; D003062:Codon / Q000235:genetics*; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D006580:Genetic Carrier Screening; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005858:Germany; D016098:Gerstmann-Straussler-Scheinker Disease / Q000235:genetics; D006801:Humans; D034062:Insomnia, Fatal Familial / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D017096:Prion Diseases / Q000235:genetics*; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*; D055815:Young Adult
chemical_list: D003062:Codon; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions