title: Transmission properties of atypical Creutzfeldt-Jakob disease: a clue to disease etiology?
abstract: The genotype at polymorphic codon 129 of the PRNP gene has a profound influence on both phenotypic expression and prion strain susceptibility in humans. For example, while the most common sporadic Creutzfeldt-Jakob disease (CJD) subtype, sporadic CJD-MM1 (M1 strain), induces a single phenotype after experimental transmission regardless of the codon 129 genotype of the recipient animal, the phenotype elicited by sporadic CJD-VV2 (V2 strain), the second most common subtype, varies according to the host codon 129 genotype. In particular, the propagation of the V2 strain in codon 129 methionine homozygotes has been linked only to acquired forms of CJD such as plaque-type dura mater graft-associated CJD (dCJD), a subgroup of iatrogenic CJD with distinctive phenotypic features, but has never been observed in sporadic CJD cases. In the present report, we describe atypical CJD cases carrying codon 129 methionine homozygosity, in a neurosurgeon and in a patient with a medical history of neurosurgery without dural grafting, showing the distinctive phenotypic features and transmission properties of plaque-type dCJD. These findings raise the possibility that the two cases, previously thought to represent sporadic CJD, might actually represent acquired CJD caused by infection with the V2 strain. Thus, careful analyses of phenotypic features and transmission properties in atypical cases may be useful to distinguish acquired from sporadic cases of CJD.
  
  
  OBJECTIVE
  Susceptibility to and phenotypic expression of Creutzfeldt-Jakob disease (CJD) depend on both the prion strain and genotype at polymorphic codon 129 of the PRNP gene. For example, propagation of the second most common sporadic CJD strain (V2 strain) into codon 129 methionine homozygotes has been linked to plaque-type dura mater graft-associated CJD (dCJD), a subgroup of iatrogenic CJD with distinctive phenotypic features, but has never been observed in sporadic CJD. In the present report, we describe atypical CJD cases in a neurosurgeon and in a patient with a medical history of neurosurgery without dural grafting, showing the distinctive phenotypic features and transmission properties of plaque-type dCJD. These findings raise the possibility that the two cases, previously considered to represent sporadic CJD, might actually represent acquired CJD caused by infection with the V2 strain.
authors.affiliation: Department of Neurological Science, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kobayashi
authors.affiliation: IRCCS, Istituto delle Scienze Neurologiche, Bologna, Italy Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Parchi
authors.affiliation: Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Laboratoire Français des Biotechnologies (LFB), Les Ulis, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Brown
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Saverioni
authors.affiliation: Influenza and Prion Disease Research Center, National Institute of Animal Health, Tsukuba, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Matsuura
authors.affiliation: Department of Neurological Science, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Takeuchi
authors.affiliation: Department of Neurological Science, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Shirou
authors.initials: S
authors.lastname: Mohri
authors.affiliation: Department of Neurological Science, Tohoku University Graduate School of Medicine, Sendai, Japan kitamoto@med.tohoku.ac.jp.
authors.forename: Tetsuyuki
authors.initials: T
authors.lastname: Kitamoto
mesh_terms: D000368:Aged; D000818:Animals; D007562:Creutzfeldt-Jakob Syndrome / Q000473:pathology / Q000635:transmission*; D004195:Disease Models, Animal; D005260:Female; D006720:Homozygote; D006801:Humans; D007049:Iatrogenic Disease; D008297:Male; D008715:Methionine / Q000235:genetics; D051379:Mice; D008875:Middle Aged; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D019635:Neurosurgical Procedures / Q000009:adverse effects; D016273:Occupational Exposure; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics* / Q000378:metabolism*; D066231:Surgeons
chemical_list: D050505:Mutant Proteins; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D008715:Methionine