title: Childhood onset in familial prion disease with a novel mutation in the PRNP gene.
abstract: BACKGROUND
  Up to 15% of cases of prion diseases are due to the autosomal dominant inheritance of coding PRNP mutations.
  
  
  OBJECTIVE
  To describe the unique clinical and genetic findings in a family of East Indian origin with autosomal dominant inheritance of a novel PRNP mutation.
  
  
  METHODS
  Detailed neurological examination and sequencing analysis of the MAPT and PRNP genes.
  
  
  METHODS
  Toronto Western Hospital, Toronto, Ontario.
  
  
  METHODS
  Five available members of a family of East Indian origin with a rapidly progressive neurodegenerative disorder characterized by dementia, motor decline, and ataxia.
  
  
  RESULTS
  We identified a novel Pro105Thr mutation in the PRNP gene in all of the 3 clinically affected family members but not in their unaffected relatives or normal controls. Although 5 of 6 affected family members had a relatively homogeneous phenotype and age at onset (range, 33-41 years), 1 of the 6 patients developed the disease at age 13 years.
  
  
  CONCLUSIONS
  A novel mutation in the PRNP gene was identified in all of the available, clinically affected members of this family with a rapidly progressive neurodegenerative disease. To our knowledge, the propositus represents the youngest individual with inherited prion disease described to date.
authors.affiliation: Centre for Research in Neurodegenerative Diseases, Department of Medicine, Toronto, Ontario, Canada.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Rogaeva
authors.forename: Cindy
authors.initials: C
authors.lastname: Zadikoff
authors.forename: Jonathan
authors.initials: J
authors.lastname: Ponesse
authors.forename: Gerold
authors.initials: G
authors.lastname: Schmitt-Ulms
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Kawarai
authors.forename: Christine
authors.initials: C
authors.lastname: Sato
authors.forename: Shabnam
authors.initials: S
authors.lastname: Salehi-Rad
authors.forename: Peter
authors.initials: P
authors.lastname: St George-Hyslop
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Lang
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000682:Amyloid / Q000235:genetics*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D017096:Prion Diseases / Q000235:genetics*; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors / Q000235:genetics*
chemical_list: D000682:Amyloid; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors