Prion mutation D178N with highly variable disease onset and phenotype

J Neurol Neurosurg Psychiatry. 2009 Mar;80(3):345-6. doi: 10.1136/jnnp.2008.149922.


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.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Alleles*
  • Chromosome Aberrations*
  • Codon / genetics*
  • Creutzfeldt-Jakob Syndrome / genetics*
  • DNA Mutational Analysis*
  • Female
  • Genes, Dominant / genetics*
  • Genetic Carrier Screening
  • Genetic Counseling
  • Genetic Predisposition to Disease / genetics
  • Germany
  • Gerstmann-Straussler-Scheinker Disease / genetics
  • Humans
  • Insomnia, Fatal Familial / genetics*
  • Male
  • Middle Aged
  • Pedigree
  • Penetrance
  • Phenotype
  • Polymorphism, Genetic / genetics
  • Prion Diseases / genetics*
  • Prion Proteins
  • Prions / genetics*
  • Young Adult


  • Codon
  • PRNP protein, human
  • Prion Proteins
  • Prions