| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
From the Department of Pathology, Case Western Reserve University* and National Prion Disease Pathology Surveillance Center, Cleveland, Ohio; the University of Utah Health Science Center, Salt Lake City, Utah; and Columbia University College of Physicians & Surgeons, New York, New York
Creutzfeldt-Jakob disease (CJD), the most common human prion disease, includes sporadic (s) and familial (f) forms. Regardless of etiology, both forms are thought to share the pathogenic mechanism whereby the cellular prion protein (PrPC) converts into its pathogenic isoform (PrPSc). While PrPC conversion is thought to be random in sCJD, conversion in fCJD is facilitated by the congenital presence of mutated PrP. Differences in PrP genotype (PRNP) and in conversion circumstances lead to PrPSc with distinct characteristics that elicit different disease phenotypes. Here, we describe a case of fCJD with a substitution of histidine (H) for arginine (R) at codon 148 (R148H) and heterozygosity of the methionine/valine (M/V) polymorphic codon 129, with the 129M allele coupled with the mutation. The disease phenotype and all major characteristics of PrPSc of fCJDR148H were virtually indistinguishable from those of sCJDMV2, which has features different from those of any other sCJD. Therefore, despite the differences in etiology, PRNP, and conversion process, the two forms of PrPSc had similar characteristics. Furthermore, comparison of fCJDR148H with a recently reported case carrying R148H and homozygosity at codon 129 suggests that codon 129 coupled with the mutation as well as that located on the normal allele can modify major phenotypic and PrPSc features of fCJDR148H.
This article has been cited by other articles:
 |
|
 |
|
  I. Cali, R. Castellani, A. Alshekhlee, Y. Cohen, J. Blevins, J. Yuan, J. P. M. Langeveld, P. Parchi, J. G. Safar, W.-Q. Zou, et al. Co-existence of scrapie prion protein types 1 and 2 in sporadic Creutzfeldt-Jakob disease: its effect on the phenotype and prion-type characteristics Brain, October 1, 2009; 132(10): 2643 - 2658. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. W. van der Kamp and V. Daggett The consequences of pathogenic mutations to the human prion protein Protein Eng. Des. Sel., August 1, 2009; 22(8): 461 - 468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Xiao, L. Miravalle, J. Yuan, J. McGeehan, Z. Dong, R. Wyza, G. T. MacLennan, A. M. Golichowski, G. Kneale, N. King, et al. Failure to Detect the Presence of Prions in the Uterine and Gestational Tissues from a Gravida with Creutzfeldt-Jakob Disease Am. J. Pathol., May 1, 2009; 174(5): 1602 - 1608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Yuan, X. Xiao, J. McGeehan, Z. Dong, I. Cali, H. Fujioka, Q. Kong, G. Kneale, P. Gambetti, and W.-Q. Zou Insoluble Aggregates and Protease-resistant Conformers of Prion Protein in Uninfected Human Brains J. Biol. Chem., November 17, 2006; 281(46): 34848 - 34858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Cali, R. Castellani, J. Yuan, A. Al-Shekhlee, M. L. Cohen, X. Xiao, F. J. Moleres, P. Parchi, W.-Q. Zou, and P. Gambetti Classification of sporadic Creutzfeldt-Jakob disease revisited. Brain, September 1, 2006; 129(Pt 9): 2266 - 2277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Basset-Leobon, E. Uro-Coste, K. Peoc'h, S. Haik, V. Sazdovitch, M. Rigal, O. Andreoletti, J.-J. Hauw, and M.-B. Delisle Familial Creutzfeldt-Jakob Disease With an R208H-129V Haplotype and Kuru Plaques. Arch Neurol, March 1, 2006; 63(3): 449 - 452. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
